Density Of Dendritic Cells Research Articles

Assessing corneal dendritic cells in glucose dysregulation small-fibre neuropathy.

Small-fibre neuropathy (SFN) is associated with glucose dysregulation, including impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Corneal confocal microscopy (CCM) offers a non-invasive tool to assess corneal nerve damage and dendritic cell density (DCD). In this study, we investigated corneal DCD in patients with SFN and glucose dysregulation, defined as IGT or T2D. We enrolled 38 patients with SFN + glucose dysregulation, 51 with SFN + non-glucose dysregulation and 20 healthy controls. All participants underwent neurological examination, neurophysiology and CCM. Individuals with SFN and glucose dysregulation had higher DCD compared with healthy controls (p = .01), and mature DCD was higher in IGT SFN patients than in T2D patients. Higher DCD in IGT compared with controls and patients with established T2D may suggest that DCD is a biomarker of early neuropathy.

Association of tear osmolarity and corneal nerves structure in dry eye disease: an in vivo study.

To evaluate the structural changes in corneal sub-basal nerves of dry eye disease (DED) patients with tear hyperosmolarity versus normosmolar tears. A prospective evaluation of the tear film (keratograph 5M), tear osmolarity, and sub-basal corneal nerves (laser scanning in-vivo confocal microscopy) was performed in a cohort of 53 DED patients (106 eyes) diagnosed as per DEWS II criteria. Patients with tear hyperosmolarity (Group 1, n = 48 eyes) were compared with DED patients without tear hyperosmolarity (Group 2, n = 58 eyes). Of 53 patients (27 females), 28 had Sjogren's syndrome, and the rest had meibomian gland dysfunction. There were more SS patients (21 vs 7) and females in Group 1. The two groups were similar in age, TMH, NIBUT, meibomian gland loss, bulbar redness, and corneal staining, except for Schirmer I (p < 0.001), and tear osmolarity (p < 0.001; worse in group 1). The groups did not differ in dendritic cell density, whether immature (53.8 vs. 38) or mature (2.7 vs. 0). The significantly different corneal nerve parameters were nerve fiber length (p = 0.005), density (p = 0.01), and branching density (p = 0.04), with lower values observed in group 1. Only tear osmolarity had a weak negative correlation with corneal nerve fiber length (r, -0.38), density (r, -0.32), and branching (r, -0.28). SS patients with hyperosmolar tears had reduced nerve fiber length and branching compared to SS patients with normosmolar tears. Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length despite similar levels of conjunctival congestion, tear film stability, and meibomian gland loss in DED patients. What is known • Corneal nerves are reduced in density and length in dry eye disease patients. • Laboratory studies have shown fragmentation of corneal nerves on exposure to hyperosmolar solutions. What is new • Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length in dry eyes compared to normosmolar tears. • The effect is independent of dendritic cell density.

Concurrent Limbal Stem Cell Deficiency and Mild Neurotrophic Keratopathy in Graft-Vs-Host Disease

Purpose: The purpose of this study was to delineate the concurrence of limbal stem cell deficiency (LSCD) and neurotrophic keratopathy in patients with ocular graft-vs-host disease (oGVHD). Methods: Medical records of patients with oGVHD were reviewed. Parameters collected included corneal sensitivity measured by using a noncontact esthesiometer, corneal fluorescein staining score (National Eye Institute grading scale), tear volume (Schirmer I test), and subbasal nerve density and limbal structure assessed by in vivo confocal microscopy. Results: Twenty-eight patients (mean age: 60.8 ± 10.4 years) with oGVHD were included; 50% (n = 14) had partial LSCD (P-LSCD), and 32% (n = 9) had complete LSCD (C-LSCD). Patients with C-LSCD showed significantly reduced total nerve density and branch nerve density compared with those with P-LSCD (P &lt; 0.02, P &lt; 0.04) and no LSCD (P &lt; 0.01, P = 0.02). Dendritic cell density was significantly higher in the C-LSCD group compared with the no LSCD group (P &lt; 0.05). Corneal sensitivity was significantly reduced in patients with C-LSCD compared with those with P-LSCD (P = 0.01) and no LSCD (P &lt; 0.02). Patients with C-LCSD had higher corneal fluorescein staining scores than patients with P-LSCD (P &lt; 0.01) and no LSCD (P = 0.02). Conclusions: This study highlights a significant concurrence of LSCD and neurotrophic keratopathy in patients with oGVHD, underscoring the link between inflammation, neurodegeneration, and loss of stem cell function.

CD8+ T cells infiltrating into tumors were controlled by immune status of pulmonary lymph nodes and correlated with non-small cell lung cancer (NSCLC) patients’ prognosis treated with chemoimmunotherapy

PurposeNeoadjuvant chemoimmunotherapy has the potential to reduce tumor burden, improve the pathological complete response (pCR) rate, and significantly prolong patients’ disease-free survival (DFS). However, the treatment’s effectiveness varies among NSCLC patients. The immunological mechanisms contributing to tumor regression still require further exploration and elucidation. MethodsThe immune status of patients’ local tumor microenvironment (TME) before and after neoadjuvant chemoimmunotherapy, their paired pulmonary lymph nodes (11th LNs) after therapy, including infiltrating immune cell densities and their correlations, were analyzed using multiplex immunofluorescence. ResultsFifty-six NSCLC patients undergoing neoadjuvant chemoimmunotherapy were enrolled and subsequently underwent surgical resection and pathological evaluation. Among these, 19 patients achieved a pCR, 6 patients exhibited a major pathological response (MPR), and 31 patients did not achieve MPR. There were no significant difference in the densities of CD8+ T cell, Treg and Dendritic cell (DC) in patients’ TME before neoadjuvant therapy (n = 26, P = 0.091, P = 0.753, P = 0.905, respectively), but after treament, these immune cells’ dynamics were significantly different between different response group. CD8+ T cell densities were increased in pCR gourp (P = 0.006), but not in non-pCR group (P = 0.389); the densities of Treg were increased in non-pCR gourp (P = 0.0004), but DC were significantly decreased in non-pCR gourp (P = 0.005). After surgery, the TME were also significantly different: patients achieving pCR typically demonstrated high densities of CD8+ T cell, DC and low densities of Tregs (P = 0.0001, P < 0.0001 and P = 0.0004). The immune status of 11th LNs also exhibited significant differences. DC densities were much higher in pCR patients, whereas Treg in the pCR group were significantly lower than those in the non-pCR group (P = 0.0008 and P = 0.003). Furthermore, the densities of DC in the TME showed a moderate positive correlation with DC in 11th LNs (P = 0.0002), while the densities of Tregs in the TME exhibited a moderate negative correlation with DC densities in 11th LNs (P = 0.03). Patients who had high densities of CD8+ T cell in the resection tissues and DC in the LNs, experienced longer DFS (P = 0.048 and P = 0.024). ConclusionImmune cells in both pulmonary LNs and the TME collectively influence the remodeling of the NSCLC patient’s TME, thus impacting treatment response and prognosis.

Sublingual immune cell clusters and dendritic cell distribution in the oral cavity.

The oral mucosa is the first line of defense against pathogenic bacteria and plays a vital role in maintaining tolerance to food antigens and commensal bacteria. We used CD11c reporter mice to visualize dendritic cells (DCs), a key immune cell population, in the oral cavity. We identified differences in DC density in each oral tissue region. Sublingual immune cell clusters (SLICs) extended from the lamina propria to the epithelium, where DCs and T cells resided in close contact with each other and innate lymphoid cells (ILCs). Targeted in situ photolabeling revealed that the SLICs comprised mostly of CD11c+CD11b+ DCs and were enriched for cDC1s and Langerhans cells. Although the frequency of T cell subsets was similar within and outside the SLICs, tissue resident memory T cells were significantly enriched within the clusters and cluster size increased in response to inflammation. Collectively, we found that SLICs form a unique microenvironment that facilitates T cell-DC interactions in the steady state and during inflammation. Since the oral mucosa is an important target for needle-free vaccination and sublingual immunotherapy to induce tolerogenic responses, the novel insight into the localized immunoregulation provided in this study may accelerate the development of these approaches.

A mathematical insight to control the disease psoriasis using mesenchymal stem cell transplantation with a biologic inhibitor

Psoriasis is a chronic, non-contagious, immune-mediated skin disorder. Inflammation of the skin’s surface is characterised by scaly white, red, or silvery spots that occur due to the hyper-proliferation of keratinocytes in the epidermal layer. Primarily, pharmaceutical drugs or immune therapy are used to treat psoriasis. We are all aware that, certain therapeutic strategies can have some adverse effects, and over time, that hidden inflammation may manifest. This article introduces a mathematical model for psoriasis, formulated by employing a set of nonlinear ordinary differential equations (ODEs) that describe the densities of T-cells, dendritic cells (DCs), keratinocytes, and mesenchymal stromal cells (MSCs) as basic cell populations. A tumor necrosis factor-α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha$$\\end{document} (TNF-α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$TNF-\\alpha$$\\end{document}) inhibitor has been imposed from the initial stage of the treatment regime, using the optimal control theoretic approach, and the numerical results have been observed. After 80 days of monitoring using only biologic TNF-α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$TNF-\\alpha$$\\end{document} inhibitors, if this approach did not provide the intended outcomes (when severity arises), stem cells are administered a few times in a pulsed manner as a cell replacement technique in addition to this anti TNF-α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$TNF-\\alpha$$\\end{document} medicine. We have observed the combined therapeutic benefit of stem cell replacement with a TNF-α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$TNF-\\alpha$$\\end{document} inhibitor from a mathematical point of view. The theoretical analysis and the numerical results revealed that stem cell transplantation, along with a TNF-α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$TNF-\\alpha$$\\end{document} inhibitor, is a promising psoriasis treatment option moving forward.

Conventional dendritic cells are more activated in the hyperplastic Thymus of myasthenia gravis patients

IntroductionDendritic cells (DCs) are crucial to form ectopic germinal centers (GCs) in the hyperplastic thymus (HT), which are typically found in anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG) patients. However, the characteristics of such DCs in the HT and their roles in thymic hyperplasia formation remain unclear. MethodsWe collected thymic tissue from MG patients and patients who underwent cardiac surgery. The tissues were cut into sections for immunohistochemistry and immunofluorescence or digested into a single cell suspension for flow cytometry. ResultsIn addition to formation of ectopic GCs, we found that the proportion of the medulla in the thymic parenchyma was higher than that in the cortex (areacortex/areamedulla, 1.279 vs. 0.6576) in the HT of MG patients. The density of conventional dendritic cells (cDCs) in the HT was 131 ± 64.36 per mm2, whereas in normal thymic tissue, the density was 59.17 ± 22.54 per mm2. The more abundant cDCs expressed co-stimulatory molecules (CD80 and CD86) strongly. Moreover, the more abundant subset was mainly CD141+ DCs (cDC1s), accounting for an increase from 15% to 29%. However, these increased cDC1s appeared to be unrelated to Hassall's corpuscles and ectopic GCs. ConclusionThymic hyperplasia in MG patients is manifested as an increase in the proportion of the thymic medulla accompanied by increases in the density and functional activation as well as changes in the subset composition of cDCs.

Confocal Microscopy of the Cornea in Aqueous-Deficient Dry Eye Disease-A Literature Review.

In vivo confocal microscopy (IVCM) is a vital tool in studying dry eye disease (DED), providing insights into morphological changes at ocular surface unit levels. This review presents the main differences in corneal structure between aqueous-deficient dry eye disease (AD-DED) and normal eyes. A comprehensive search of PubMed, Web of Science, Embase, and MEDLINE databases from January 2000 to December 2023 was conducted. The study selection process, as well as data selection and examination, were independently performed by two members of the review team. The review reveals a consistent decrease in corneal surface epithelial cell density in AD-DED cases compared to a control group, but conflicting data on basal epithelial cell density. Notably, the abnormal hyperreflectivity of keratocytes in patients with Sjogren's syndrome was recorded, and there was a significant keratocyte density in AD-DED subjects compared to evaporative DED and control groups. Studies also found a decrease in sub-basal nerve density, increased tortuosity, and the fragmentation of nerve fibers. Dendritic cell density and dendritic cell dendrites increase in AD-DED patients compared to healthy subjects. IVCM is a powerful tool for enhancing our understanding of the pathophysiological mechanisms underlying DED. However, the review underscores the urgent need to standardize the terminology, analysis, and units used for accurate interpretation, a crucial step in advancing our knowledge of DED.

Corneal nerve fiber morphology following COVID-19 infection in vaccinated and non-vaccinated population

To examine corneal subbasal nerve changes in patients who received vaccination against SARS-CoV-2 virus and underwent COVID-19 infection compared to infected non-vaccinated patients and healthy controls. Twenty-nine eyes of 29 vaccinated patients (mean age: 36.66 ± 12.25 years) within six months after PCR or Ag test proven COVID-19 infection and twenty-eight eyes of 28 age-matched infected, non-vaccinated patients (mean age: 42.14 ± 14.17 years) were enrolled. Twenty-five age-matched healthy individuals (mean age: 47.52 ± 18.45 years) served as controls. In vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module, Germany) was performed in each group. Corneal subbasal nerve plexus morphology and corneal dendritic cells (DC) were evaluated. Significantly higher corneal nerve fiber density (P < 0.001), nerve branch density (P < 0.001), nerve fiber length (P < 0.001), total branch density (P = 0.007), nerve fiber area (P = 0.001) and fractal dimension (P < 0.001) values were observed in vaccinated patients after COVID-19 infection compared to the non-vaccinated group. Significantly higher DC density was observed in the non-vaccinated group compared to the control group (P = 0.05). There was a statistically significant difference in the size of mature DCs (P < 0.0001) but the size of immature DCs did not differ significantly among the 3 groups (P = 0.132). Our results suggest that SARS-CoV-2 vaccination may have a protective effect against the complications of COVID-19 disease on the corneal subbasal nerve fibers.

Impact of tertiary lymphoid structures in response to immune checkpoint blockade in patients with head and neck squamous cell carcinoma.

e18021 Background: Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yetefficacy remains low. Current assessment for tumor response relies on a single proportional biomarker expressed in immune and tumor cells (Combined Positive Score, CPS) without differentiation by cell type, potentially explaining its limited predictive value. Tertiary Lymphoid Structures (TLS) have shown a stronger association with improved ICB response than PD-L1. However, their exact composition, size, and spatial biology in HNSCC remain understudied, and there is a need for a deeper examination of TLS biology in HNSCC and its link with clinical response to ICB. Methods: Pre-ICB tumor tissue sections (formalin-fixed, paraffin-embedded) were obtained from 10 responders (complete response, partial response, or stable disease) and 10 non-responders to ICB (progressive disease). A custom multi-immunofluorescence (mIF) staining assay was designed, optimized, and applied to characterize tumor cells (pan-cytokeratin), T cells (CD4, CD8), B cells (CD19, CD20), myeloid cells (CD16, CD56, CD163), dendritic cells (LAMP3), fibroblast (alpha Smooth Muscle Actin), proliferative status (Ki67) and immunoregulatory molecules (PD1). Following imaging and tissue classification using machine learning techniques, spatial profiling was performed, including proximity, density, and infiltration analysis. Response status was assessed via RECIST 1.1. Spatial metrics were compared among groups based on response to ICB. An unpaired t-test was used to compare mean densities. Multivariable logistic regression was used to measure the effect of TLS size on achieving response to ICB (CR, PR or SD). Results: A higher density of dendritic cells (LAMP3) was found in responders compared to non-responders to ICB (p=0.0415). A positive correlation was observed between mIF and pathologist identification of TLS (r2=0.51; p=0.0039). TLS trended toward more prevalent in responders to ICB (p=0.0906). There was no association of high CPS (&gt;20) with improved PFS (HR=0.91; p-value=0.8538 C.I.= 0.3538-2.369). Multivariate logistic regression analysis showed that total TLS area &gt; 5.8 (mm²) (mean TLS size in this cohort) in pretreatment tissue biopsies was associated with 2.4 increased odds of achieving objective response (OR= 2.4, p=0.05, 95% C.I.=1.2-275.1) independent of CPS score. Conclusions: Tertiary Lymphoid Structures play a critical role in the immune response to HNSCC, are quantifiable through histopathologic assessment by a pathologist, and may potentially outperform CPS as a predictor of ICB response.

Alterations in the Ocular Surface and Corneal Subbasal Nerve Plexus Following Various Retinal Surgical Procedures: A One-Year Confocal Microscopy Prospective Study.

To evaluate the effects of retinal surgery on the ocular surface and corneal subbasal nerve plexus (SNP). Ninety-eight patients undergoing 23-gauge pars plana vitrectomy for various vitreoretinal disorders were prospectively studied. We collected detailed operative and perioperative data, measuring dry eye syndrome (DED) severity and Ocular Surface Disease Index (OSDI) scores before surgery and at postoperative intervals. In vivo confocal microscopy (IVCM) quantified SNP and dendritic cell (DC) densities. Fifty-three patients were analyzed. Post-surgery, OSDI scores rose from a baseline of 5.5 ± 3.5 to 12.24 ± 6.5 at one month, later reducing to 7.8 ± 4.0 after a year. DED severity increased from 0.6 ± 0.6 initially to 1.6 ± 0.6 at three months, returning to near baseline (0.9 ± 0.6) one year after surgery. DC densities increased notably by the third (58.85 ± 75.6 cells/mm²) and ninth (59.95 ± 86 cells/mm²) postoperative months, especially in patients undergoing combined phacoemulsification, vitrectomy, and C3F8 gas tamponade. SNP parameters, particularly nerve fiber density and length, showed significant declines one month post-surgery, not recovering to baseline levels within a year. Fiber density dropped from 19.06 ± 8.3 fibers/mm² preoperatively to 4.68 ± 4.8 fibers/mm² at one month, partially recovering to 10.64 ± 8.2 fibers/mm² at twelve months. Fiber length decreased from 13.31 ± 3.2 mm/mm² to 6.86 ± 3.4 mm/mm² at one month, later improving to 9.81 ± 4.5 mm/mm² at twelve months, notably in patients with silicone oil (SiO2) tamponade. Retinal surgery, especially when combined with phacoemulsification and C3F8 or SiO2 tamponade, significantly affects ocular surface integrity and SNP density, with these changes lasting up to a year. Expanded studies with more patients and longer follow-up, using finer 25- and 27-gauge vitrectomy tools, are recommended to confirm and extend these findings.

Analysis of the mucosal chemokines CCL28, CXCL14, and CXCL17 in dry eye disease: An in vitro and clinical investigation

Mucosal chemokines have antimicrobial properties and play an important role in mucosal immunity. However, little is known about their expression on the ocular surface. This study aimed to analyze the expression of the mucosal chemokines CCL28, CXCL14 and CXCL17 in corneal and conjunctival epithelial cells under in vitro dry eye (DE) conditions, and in conjunctival samples from healthy subjects and DE patients. Human corneal epithelial cells (HCE) and immortalized human conjunctival epithelial cells (IM-HConEpiC) were incubated under hyperosmolar (400–500 mOsM) or inflammatory (TNF-α 25 ng/mL) conditions for 6 h and 24 h to measure CCL28, CXCL14, and CXCL17 gene expression by RT-PCR and their secretion by immunobead-based analysis (CCL28, CXCL14) and ELISA (CXCL17). Additionally, twenty-seven DE patients and 13 healthy subjects were included in this study. DE-related questionnaires (OSDI, mSIDEQ and NRS) evaluated symptomatology. Ocular surface integrity was assessed using vital staining. Tactile sensitivity was measured with Cochet-Bonnet esthesiometer, and mechanic and thermal (heat and cold) sensitivity using Belmonte's non-contact esthesiometer. Subbasal nerve plexus and dendritic cell density were analyzed by in vivo confocal microscopy. Conjunctival cells from participants were collected by impression cytology to measure mucosal chemokines gene expression by RT-PCR. Our results showed that HCE and IM-HConEpiC cells increased CCL28, CXCL14, and CXCL17 secretion under hyperosmolar conditions. The gene expression of CCL28 was significantly upregulated in conjunctival samples from DE patients. CCL28 expression correlated positively with symptomatology, corneal staining, heat sensitivity threshold, and dendritic cell density. CXCL14 expression correlated positively with age, ocular pain, conjunctival staining, tactile sensitivity, and image reflectivity. CXCL17 expression correlated positively with corneal staining. These results suggest that corneal and conjunctival epithelial cells could be a source of CCL28, CXCL14, and CXCL17 on the ocular surface and that CCL28 might be involved in DE pathogenesis.

Efficacy of 2% Hydroxypropyl Methylcellulose and Bandage Contact Lens for the Management of Dry Eye Disease after Cataract Surgery

Objectives. To investigate the effect of 2% hydroxypropyl methylcellulose (HPMC) and bandage contact lens (BCL) on dry eye disease after cataract surgery. Methods. This prospective randomized controlled trial included 63 eyes which were divided into the balanced salt solution (BSS), HPMC, BCL, and combined HPMC and BCL (H&amp;B) groups. The Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), and average tear break-up time were measured before cataract surgery and 30 days postoperatively. Differences in corneal nerve fiber (CNF) and dendritic cell (DC) density in various directions were evaluated and compared. The CNFs and DCs in central and infratemporal directions were observed using in vivo confocal microscopy. Data were evaluated using the Kruskal–Wallis rank-sum test and analysis of variance. Results. The differences in variations in OSDI and TMH after cataract surgery between the four groups were statistically significant (P&lt;0.05). The postoperative OSDI of the HPMC group decreased compared with their preoperative OSDI. A statistically significant difference in the variations of OSDI score was observed between the HPMC and other groups (P&lt;0.05). The postoperative variations in TMH in the HPMC group were significantly higher than those observed preoperatively and significantly differed between HPMC and BCL groups and between BCL and H&amp;B groups (P&lt;0.05). Postoperatively, the density of corneal DCs decreased in BSS and HPMC groups and increased in BCL and H&amp;B groups (P&lt;0.001). Conclusions. The application of 2% HPMC in cataract surgery has a certain effect on managing dry eye after cataract surgery. Although the use of BCLs after cataract surgery has some benefits, it may cause mild ocular surface inflammation. Nevertheless, using 2% HPMC with BCLs in the perioperative phase of cataract surgery can alleviate the subjective discomfort of patients and can safely and effectively replace eye patch after cataract surgery.

Neuroinflammatory findings with corneal COnfocal microscopy in long COVID‐19 patients, 2 years after acute SARS‐CoV‐2 infection

Purpose: To describe corneal confocal microscopy findings in patients with long COVID‐19 with persistent symptoms over 20 months after SARS‐CoV‐2 infection.Methods: Cross‐sectional comparative transversal study that included a total of 53 patients, 33 patients with Long COVID‐19 and 22 controls matched in age and gender. Long COVID‐19 diagnosis was established according to the World Health Organization criteria Corneal confocal microscopy Heidelberg Retina Tomograph II (Heidelberg Engineering, Heidelberg, Germany) was performed to evaluate sub‐basal nerve plexus morphology (corneal nerve fibre density, nerve fibre length, nerve branch density, nerve fibre total branch density, nerve fibre area, and nerve fibre width). Dendritic cells density and area, along with microneuromas and other morphological changes of the nerve fibres were recorded.Results: Long COVID‐19 patients presented reduced corneal nerve density and branch density as well as shorter corneal nerves compared to the control group. Additionally, Long COVID‐19 patients showed an increased density of Dendritics Cells with also greater area than that found in the control group of patients without systemic diseases. Microneuromas were detected in 24.2% of Long COVID‐19 patients.Conclusions: Long COVID‐19 patients exhibited altered corneal nerve parameters and increased DC density over 20 months after acute SARS‐CoV‐2 infection. These findings are consistent with a neuroinflammatory condition hypothesized to be present in patients with long COVID‐19, highlighting the potential role of corneal confocal microscopy as a promising noninvasive technique for the study of patients with long COVID‐19.

Dendritic cell-based immunotherapy in non-small cell lung cancer: a comprehensive critical review.

Despite treatment advances through immunotherapies, including anti-PD-1/PD-L1 therapies, the overall prognosis of non-small cell lung cancer (NSCLC) patients remains poor, underscoring the need for novel approaches that offer long-term clinical benefit. This review examined the literature on the subject over the past 20 years to provide an update on the evolving landscape of dendritic cell-based immunotherapy to treat NSCLC, highlighting the crucial role of dendritic cells (DCs) in immune response initiation and regulation. These cells encompass heterogeneous subsets like cDC1s, cDC2s, and pDCs, capable of shaping antigen presentation and influencing T cell activation through the balance between the Th1, Th2, and Th17 profiles and the activation of regulatory T lymphocytes (Treg). The intricate interaction between DC subsets and the high density of intratumoral mature DCs shapes tumor-specific immune responses and impacts therapeutic outcomes. DC-based immunotherapy shows promise in overcoming immune resistance in NSCLC treatment. This article review provides an update on key clinical trial results, forming the basis for future studies to characterize the role of different types of DCs in situ and in combination with different therapies, including DC vaccines.

Corneal complications of ocular GvHD

Corneal fluorescein staining is one of the tests recommended to diagnose and grade ocular graft versus host disease (GvHD) according to the International Chronic Ocular GvHD Consensus Group. Despite superficial punctate keratopathy is the most common corneal manifestation, patients with more severe stages may develop corneal neovascularization, sterile corneal ulceration and even perforation. Previous in vivo confocal microscopy (IVCM) studies reported significant microstructural changes in the cornea of patients with ocular GvHD, including a higher density of dendritic cells and globular immune cells, a network of hyper‐reflective activated keratocytes, and a lower density and higher tortuosity of sub‐basal corneal nerves. Dendritic cells act as antigen‐presenting cells, and play a key role in ocular surface immune homeostasis. Thus, their increased density may be indicative of immune activation and inflammation of the ocular surface in patients with ocular GvHD. Interestingly, Kheirkhah et al. reported higher dendritic cell density in patients with DED owing to systemic immune disease (i.e., Sjögren syndrome and ocular GvHD) compared to patients with DED of other origins. Recently, our group employed a fully automated IVCM analysis system to compare corneal sub‐basal nerve plexus in patients with DED owing to both ocular GvHD and Sjögren syndrome and in healthy control subjects. Although overall patients with DED showed lower density of nerve fibres and branches, shorter nerve fibres and higher fibre width compared to healthy controls, no significant difference was observed between patients with ocular GvHD and Sjögren syndrome for all IVCM metrics. In agreement with this observation, other studies reported no significant difference of IVCM parameters in DED patients with and without ocular GvHD after adjusting for clinical severity of dry eye. This suggests that the ocular surface changes observed by IVCM in ocular GvHD may be possibly reflective of the local disease severity rather than the underlying systemic process.

Analysis of the ocular surface functional unit in episodic migraine

AimMigraine is a chronic neurovascular disease that affects the trigeminovascular system. The purpose of this study was to evaluate corneal subbasal nerve fibers, dendritic cells and to measure tear film parameters in migraine.Patients and methods87 eyes of 44 patients suffering from migraine with a mean age of 33.23 ± 11.41 years were included in our study. 25 age-matched controls (mean age of 30.16 ± 12.59 years; P = 0.162) were recruited. The corneal subbasal plexus and the dendritic cells (DC) were analyzed using in vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module; Heidelberg Engineering GmbH), and the tear film was imaged using LacryDiag (Quantel Medical, France).ResultsRegarding the subbasal nerve fibers of the cornea, none of the examined parameters differed significantly in migraine patients from controls. We found a significant increase in the corneal DC density (P < 0.0001) and DC area (P < 0.0001) in migraine patients compared to healthy volunteers. DC density showed a positive correlation with the monthly attack frequency (r = 0.32, P = 0.041) and the DC area a negative correlation with corneal nerve branch density (r = -0.233, P = 0.039), nerve fiber length (r = -0.232, P = 0.04) and total branch density (r = -0.233, P = 0.039). Using LacryDiag a significant loss of Meibomian gland area could be detected on the superior eyelid (P = 0.005) in migraine.ConclusionsOur results suggest the presence of neuroinflammation in the cornea of migraine patients affecting the peripheral trigeminal system. Dendritic cells surrounding the subbasal plexus may be involved in the activation and modulation of pain in migraine.

Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis.

In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively. Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 μm2 ). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 μm) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls. In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03). Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.

Relation Between Corneal Dendritic Cell Density and Tear Film Stability in Patients with Epidemic Keratoconjunctivitis Associated Dry Eye

Purpose To clarify the ocular surface features of patients with recent history of epidemic keratoconjunctivitis (EKC) and the relation between corneal dendritic cells (DCs) and ocular discomfort. Methods Normal controls (NC) and dry eye (DE) patients without EKC were recruited. Patients with recent EKC history (onset >4 weeks, but <20 weeks) were recruited as EKC + DE group (with dry eye) or EKC–DE group (without dry eye). Ocular surface disease index (OSDI) questionnaire, tear film parameters including lipid layer thickness, first tear break-up time (fBUT), average tear break-up time (aBUT), tear meniscus height and Schirmer I test, meibomian gland parameters, and in vivo corneal confocal microscopy were evaluated. Results 50 subjects in the NC group, 83 patients in the DE group, 76 patients in the EKC + DE group, and 38 patients in the EKC–DE group were included. Compared with the NC, DE, and EKC–DE groups, the EKC + DE group represented higher OSDI, lid margin, and meibum score (p < 0.05). In the EKC + DE group, the tear volume (10.5 ± 3.7 mm) was significantly higher than in the DE group (8.1 ± 2.8 mm, p < 0.001). The DC density in the EKC + DE group (29.98 ± 15.38 cells/image) was significantly higher than in NC, DE, and EKC–DE groups (4.68 ± 4.05 cells/image) (p < 0.001). The DC density was positively correlated with OSDI, lid margin, and meibum score (all p < 0.01) while inversely correlated with fBUT, aBUT (all p < 0.001) in the EKC + DE group. Conclusions Corneal DC density significantly correlates to ocular discomfort and tear film instability in patients with recent EKC history who suffer from DE without aqueous tear deficiency.

Neuroinflammatory Findings of Corneal Confocal Microscopy in Long COVID-19 Patients, 2 Years after Acute SARS-CoV-2 Infection.

To describe corneal confocal microscopy findings in patients with long COVID-19 with persistent symptoms over 20 months after SARS-CoV-2 infection. A descriptive cross-sectional study that included a total of 88 patients; 60 patients with Long COVID-19 and 28 controls. Long COVID-19 diagnosis was established according to the World Health Organization criteria. Corneal confocal microscopy using a Heidelberg Retina Tomograph II (Heidelberg Engineering, Heidelberg, Germany) was performed to evaluate sub-basal nerve plexus morphology (corneal nerve fiber density, nerve fiber length, nerve branch density, nerve fiber total branch density, nerve fiber area, and nerve fiber width). Dendritic cell density and area, along with microneuromas and other morphological changes of the nerve fibers were recorded. Long COVID-19 patients presented with reduced corneal nerve density and branch density as well as shorter corneal nerves compared to the control group. Additionally, Long COVID-19 patients showed an increased density of dendritic cells also with a greater area than that found in the control group of patients without systemic diseases. Microneuromas were detected in 15% of Long COVID-19 patients. Long COVID-19 patients exhibited altered corneal nerve parameters and increased DC density over 20 months after acute SARS-CoV-2 infection. These findings are consistent with a neuroinflammatory condition hypothesized to be present in patients with Long COVID-19, highlighting the potential role of corneal confocal microscopy as a promising noninvasive technique for the study of patients with Long COVID-19.