Immature Dendritic Cells Research Articles

Combining galacto-oligosaccharides and 2'-fucosyllactose alters their fermentation kinetics by infant fecal microbiota and influences AhR-receptor dependent cytokine responses in immature dendritic cells.

Galacto-oligosaccharides (GOS) and 2′-fucosyllactose (2′-FL) are non-digestible carbohydrates (NDCs) that are often added to infant formula to replace the functionalities of human milk oligosaccharides (HMOs). It is not known if combining GOS and 2′-FL will affect their fermentation kinetics and subsequent immune-modulatory effects such as AhR-receptor stimulation. Here, we used an in vitro set-up for the fermentation of 2′-FL and GOS, either individually or combined, by fecal microbiota of 8-week-old infants. We found that GOS was fermented two times faster by the infant fecal microbiota when combined with 2′-FL, while the combination of GOS and 2′-FL did not result in a complete degradation of 2′-FL. Fermentation of both GOS and 2′-FL increased the relative abundance of Bifidobacterium, which coincided with the production of acetate and lactate. Digesta of the fermentations influenced dendritic cell cytokine secretion differently under normal conditions and in the presence of the AhR-receptor blocker CH223191. We show that, combining GOS and 2′-FL accelerates GOS fermentation by the infant fecal microbiota of 8-week-old infants. In addition, we show that the fermentation digesta of GOS and 2′-FL, either fermented individually or combined, can attenuate DC cytokine responses in a similar and in an AhR-receptor dependent way.

MiR-195-3p is a Novel Prognostic Biomarker Associated with Immune Infiltrates of Lung Adenocarcinoma.

BackgroundMicroRNA-195-3p (miR-195-3p) plays an important role in some tumors, but its role in LUAD is unclear. This study explored the expression of miR-195-3p in LUAD and the relationship between the expression of miR-195-3p and the clinical and prognostic characteristics of LUAD patients.MethodsMiR-195-3p expression and clinical information of LUAD patients were obtained from The Cancer Genome Atlas (TCGA). Kruskal–Wallis test, Wilcoxon signed rank test, logistic regression, and Cox regression were used to assess the relationship between the expression level of miR-195-3p and clinical features in LUAD tissues. Kaplan–Meier survival curves were used to analyze the effect of miR-195-3p expression levels on the prognosis of LUAD patients. Target genes of miR-195-3p were predicted by several software. GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), and immune infiltration analysis were used to analyze the possible regulatory network of miR-195-3p.ResultsCompared with normal lung tissue, miR-195-3p is down expressed in LUAD tissue (P < 0.001). The low miR-195-3p expression in LUAD was significantly associated with N stage (P = 0.046), pathologic stage (P = 0.011), and gender (P = 0.010). Low miR-195-3p expression predicted a poorer overall survival (HR: 0.60; 95% CI: 0.45–0.81; P = 0.001) and disease-specific survival (HR: 0.55; 95% CI: 0.37–0.80; P = 0.002). The expression of miR-195-3p (HR: 0.488; 95% CI: 0.304–0.784; P = 0.003) was independently correlated with OS in LUAD patients. High expression of miR-195-3p genes, including ABCC2, AGMAT, ARNTL2, ATP6V0A4, CDC25A, CDK1, FAM111B, GJB2, GRIP1, HMGA2, HOXA9, KIF14, SYT2, and TFAP2A, were associated with poor OS in LUAD. GO and KEGG analysis suggested that miR-195-3p was related to the phagosome pathway. MiR-195-3p may promote the function of B cells, dendritic cells, eosinophils, immature dendritic cells, macrophages, Mast cells, NK cells, plasmacytoid dendritic cells, and follicular helper T cells.ConclusionLow miR-195-3p expression is significantly associated with poor survival in LUAD, which may be a promising prognostic biomarker for LUAD.

Dendritic Cell Subsets: The Next Target for Pregnant Complications?

Dendritic cells (DCs) are professional antigen-presenting cells with both immune stimulatory and regulatory functions. DCs are critical players in pregnancy, whose dysregulation is associated with multiple pregnancy-related complications. According to recently reported findings, this review aimed to elaborate the effects of subsets of DCs on gestation, including plasmacytoid DCs (pDCs), conventional DCs (cDCs), immature DCs (iDCs), and mature DCs (mDCs). The present review clearly illustrate that the subsets of DCs, the spatial-temporal regulation of DCs during pregnancy, the balance of pDCs/cDCs ratio influenced the pregnancy outcomes, and the balance of iDCs/mDCs ratio influenced the pregnancy outcomes. &nbsp;The possibility of targeting DC subsets for the treatment of pregnancy-related complications and eliminating the remaining gaps were discussed. A deeper understanding of DC subsets regulation during pregnancy can significantly contribute to the clinical application of these cells.

The Mechanism of Delayed Ischemic Preconditioning in Alleviating Acute Ischemia/Reperfusion Renal Injury through Treg Mediated by Immature CD11c+ Dendritic Cells

Introduction: Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury, and its mechanism is complex involving multiple factors, while delayed ischemic preconditioning (DIPC) has a protective effect on the above process. In our previous study, we found that DIPC can exert its protection on renal IRI by inhibiting the maturation of dendritic cells (DCs), but the mechanism has not been clarified. This study aimed to investigate the protective mechanism of DIPC on renal IRI in mice through Treg mediated by immature DCs (imDCs). Methods: The IRI mice model, DIPC treatment, and conditional CD11c⁺ DCs (CD11c-DTR) knockout mice were used to perform our study. The maturation and differentiation of DCs and Treg cells in the kidney and spleen were analyzed by flow cytometry. HE staining was used to evaluate the pathology of the kidney tissue. The level of creatinine (Cr), oxidative stress factors (SOD, MDA), and inflammatory factors (TNF-α, IL-10, IL-4) were also measured. Then, imDCs were co-cultured with HK-2 cells, and apoptosis was analyzed with flow cytometry and PI-Hoechst 33,342 fluorescence staining to assess the apoptosis rate of HK-2 cells under hypoxic-reoxygenated (H/R) conditions. Results: DIPC could decrease renal Cr levels, alleviate pathological renal damage, and reduce oxidative stress and inflammation caused by IRI. Moreover, DIPC could decrease the number of mature DCs (mDCs) and increase Treg lymphocyte infiltration in the kidney tissue, while the reduction of DCs reversed this process. In addition, our in vitro experiment found that in the H/R model, the apoptosis of HK-2 cells decreased which were co-cultured with imDCs. Conclusion: DIPC can regulate the differentiation of DCs into imDCs, thus affecting the differentiation level and distribution of Treg cells to exert its protective effect on renal IRI.

Complexity of Secretory Chemokines in Human Intestinal Organoid Cultures Ex Vivo.

Complexity of Secretory Chemokines in Human Intestinal Organoid Cultures Ex Vivo.

Elucidated pathogenesis and therapeutic prospects in Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is characterized by immature dendritic cell proliferation, which is currently classified as an inflammatory myeloid neoplasm. Clinical features and outcomes vary from spontaneously regressing isolated bone disease to fatal liver, spleen, or hematopoietic system (risk organ) involvement-positive multisystem disease. LCH cells have the only mutation in the mitogen-activated protein kinase (MAPK) signaling pathway gene, represented by the BRAF V600E mutation, which is the driver mutation. The type of disease depends on the stage of hematopoietic cell differentiation at which the mutation occurs. LCH cells acquire anti-apoptosis and senescence-associated secretory phenotype by oncogene-induced senescence, with migration failure to lymph nodes. These cause LCH cell accumulation and various inflammatory cell recruitment in the lesion, resulting in severe inflammation. Tissue damage in LCH is due to this inflammation, not the LCH cell proliferation. Patients with a risk of organ involvement without the initial treatment response may be rescued by allogeneic hematopoietic stem cell transplantation after reducing the disease activity with MAPK inhibitors. Intravenous zoledronic acid and intrathecal cytarabine injections have been introduced into the ongoing clinical trial in Japan to reduce bone recurrence and prevent neurodegeneration as sequelae.

Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status.

Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer.Objective:To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection.Methodology:CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018).Results:There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004).Conclusion:Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

A novel coculture system for assessing respiratory sensitizing potential by IL-4 in T cells.

Although several in vitro assays that predict the sensitizing potential of chemicals have been developed, none can distinguish between chemical respiratory and skin sensitizers. Recently, we established a new three-dimensional dendritic cell (DC) coculture system consisting of a human airway epithelial cell line, immature DCs derived from human peripheral monocytes, and a human lung fibroblast cell line. In this coculture system, compared to skin sensitizers, respiratory sensitizers showed enhanced mRNA expression in DCs of the key costimulatory molecule OX40 ligand (OX40L), which is important for T helper 2 (Th2) cell differentiation. Herein, we established a new two-step DC/T cell coculture system by adding peripheral allogeneic naïve CD4+ T cells to the DCs stimulated in the DC coculture system. In this DC/T cell coculture system, model respiratory sensitizers, but not skin sensitizers, enhanced mRNA expression of the predominant Th2 marker interleukin-4 (IL-4). To improve the versatility, in place of peripheral monocytes, monocyte-derived proliferating cells called CD14-ML were used in the DC coculture system. As in peripheral monocytes, enhanced mRNA expression of OX40L was induced in CD14-ML by respiratory sensitizers compared to skin sensitizers. When these cell lines were applied to the DC/T cell coculture system with peripheral allogeneic naïve CD4+ T cells, respiratory sensitizers but not skin sensitizers enhanced the mRNA expression of IL-4. Thus, this DC/T cell coculture system may be useful for discriminating between respiratory and skin sensitizers by differential mRNA upregulation of IL-4 in T cells.

Exosomes with FOXP3 from gene-modified dendritic cells ameliorate the development of EAE by regulating the balance of Th/Treg.

Objective: To investigate the efficiency and potential mechanisms of exosomes from dendritic cells (DCs) transfected with Forkhead box protein P3 (FOXP3) in the development of experimental autoimmune encephalomyelitis (EAE).Method: Mouse bone marrow-derived immature DCs were loaded with adenovirus carrying FOXP3 gene, and exosomes were generated. Then the exosomes with FOXP3 (FOXP3-EXOs) were co-cultured with CD4+T cell in vitro to evaluate their potential on CD4+T cell proliferation and differentiation, and injected into EAE mice to assess their effects on the development of EAE.Result: FOXP3-EXOs were effective to inhibit the CD4+T cell proliferation and the production of Interferon gamma (IFN-γ), interleukin (IL)-6, and IL-17, while they promoted the production of IL-10 in vitro. Moreover, FOXP3-EXOs treatment significantly decreased the neurological scores, reduced the infiltration of inflammatory cells into the spinal cord, and decreased demyelination in comparison to saline and Con-EXOs treated EAE mice. Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice.Conclusion: The present study preliminarily investigated the effects and potential mechanisms of FOXP3-EXOs in EAE and revealed that the FOXP3-EXOs could inhibit the production of Th1 and Th17 cells and promote the production of Treg cells as well as ameliorate the development of EAE. The neuroprotective effects of FOXP3-EXOs on EAE are likely due to the regulation of Th/Treg balance.

Microarray analysis to explore the effect of CXCL12 isoforms in a pancreatic pre-tumor cell model.

CXCL12 expression was significantly lower in tumor samples than in corresponding normal samples. CXCL12 expression was significantly positively related to the infiltration levels of T cells, dendritic cells (DCs), immature DCs, cytotoxic cells, Tfh cells, mast cells, B cells, Th1 cells, natural killer (NK) cells, pDCs, neutrophils, and T helper cells (Spearman correlation coefficient > 0.5, P < 0.001) and negatively correlated with the infiltration level of NK CD56bright cells. In addition, pancreatic hTERT-HPNE cells treated with three diverse CXCL12 isoforms exhibited changes mainly in the regulation of the epithelial-mesenchymal transition activation pathway.

Identification of Profound Metabolic Alterations in Human Dendritic Cells by Progesterone Through Integrated Bioinformatics Analysis.

Maintaining the homeostasis of the decidual immune microenvironment at the maternal-fetal interface is essential for reproductive success. Dendritic cells (DCs) are the professional antigen-presenting cells and dominate this balance of immunogenicity and tolerance. Progesterone (P4) is highlighted as the “hormone of pregnancy” in most eutherian mammals because of its regulatory role in immune-endocrine behavior during pregnancy. Recent studies have shown that P4 is associated with the differentiation and function of DCs, however, the underlying mechanisms remain unidentified. In addition, while progress in the field of immunometabolism has highlighted the intimate connections between the metabolism phenotype and the immunogenic or tolerogenic fate of DCs, whether P4 can affect DCs metabolism and thus exert a functional manipulation has not yet been explored. In this study, we acquired human peripheral blood monocyte-derived DCs and conducted RNA sequencing (RNA-seq) on immature DCs (iDCs), P4-treated DCs (pDCs), and mature DCs (mDCs), aiming to comprehensively assess the effects of P4 on DCs. Our results showed pDCs performed a distinct differentially expressed genes (DEGs) profile compared with iDCs or mDCs. Further functional enrichment and weighted gene co-expression network (WGCNA) analysis found that these DEGs were related not only to the cellular components but also to the significant metabolic activities, including mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid metabolism. In addition, these changes may be involved in the activation of various signaling pathways of PI3K/Akt/mTOR, AMPK/PGC1-α, and PPAR-γ. In summary, our work suggested that P4 induced profound metabolic alterations of mitochondrial OXPHOS and fatty acid metabolism in DCs. Our findings may provide new insights into the role of P4 in DCs.

Dendritic cells maturation facilitated by group-adjustable lipopolysaccharide analogues synthesized via RAFT polymerization

Transforming immature DCs into mature state to activate cellular immunity is a critical step in initiating immunoprophylaxis and immunotherapy. Lipopolysaccharides (LPS) can promote DCs maturation by binding receptor on DCs surface, but their clinical application is limited due to biological toxicity. Although many LPS analogues have been developed, complex synthesis and purification hinder their practical application. Here, we propose a novel and simple strategy to synthesize LPS analogues with adjustable structural units. Using monomer units similar to the key functional groups of LPS, we synthesize LPS analogues with different group ratios by RAFT polymerization. The obtained analogues have little negative effect on cell viability. Compared with LPS, the analogues show greater promoting effect on DCs maturation. And the analogues can be applied to different scenarios since the degrees of promoting DCs maturation by LPS analogues with different group ratios are different. This strategy provides a new direction for synthesizing LPS analogues, and it has the potential to produce LPS analogues on a large scale with tunable promoting DCs maturation effect.

Enhancement of the Anti-Angiogenic Effects of Delphinidin When Encapsulated within Small Extracellular Vesicles.

(1) Background: The anthocyanin delphinidin exhibits anti-angiogenic properties both in in vitro and in vivo angiogenesis models. However, in vivo delphinidin is poorly absorbed, thus its modest bioavailability and stability reduce its anti-angiogenic effects. The present work takes advantage of small extracellular vesicle (sEV) properties to enhance both the stability and efficacy of delphinidin. When encapsulated in sEVs, delphinidin inhibits the different stages of angiogenesis on human aortic endothelial cells (HAoECs). (2) Methods: sEVs from immature dendritic cells were produced and loaded with delphinidin. A method based on UHPLC-HRMS was implemented to assess delphinidin metabolites within sEVs. Proliferation assay, nitric oxide (NO) production and Matrigel assay were evaluated in HAoECs. (3) Results: Delphinidine, 3-O-β-rutinoside and Peonidin-3-galactoside were found both in delphinidin and delphinidin-loaded sEVs. sEV-loaded delphinidin increased the potency of free delphinidin 2-fold for endothelial proliferation, 10-fold for endothelial NO production and 100-fold for capillary-like formation. Thus, sEV-loaded delphinidin exerts effects on the different steps of angiogenesis. (4) Conclusions: sEVs may be considered as a promising approach to deliver delphinidin to target angiogenesis-related diseases, including cancer and pathologies associated with excess vascularization.

LB19. Intramuscular therapeutic immunization targeting RelMtb/MIP-3 induces immune signatures associated with better TB control in vivo compared to

BackgroundTuberculosis (TB) is one of the leading causes of death from a single infectious agent worldwide. The lengthy treatment regimen reflects the unique ability of a subpopulation of “persister” bacteria to remain in a nonreplicating state in the infected host through various adaptive strategies, including induction of the stringent response. The key stringent response enzyme, RelMtb, is essential for long-term Mycobacterium tuberculosis (Mtb) survival under physiologically relevant stresses in vitro and in animal lungs. Recently, our group has generated a therapeutic, parenteral, relMtb DNA vaccine, which induces RelMtb-specific cellular immunity and augments the activity of the first-line drug isoniazid against active TB in mice and guinea pigs. Our group also has applied a novel vaccination strategy involving the fusion of an antigen of interest with the immature dendritic cell (iDC)-targeting chemokine MIP-3α/CCL20, which significantly enhances antigen-specific T-cell responses. We sought to determine if this iDC-targeting strategy improves the immunogenicity of the therapeutic relMtb DNA vaccine.MethodsWe cloned the relMtb and chemokine MIP-3α genes into the eukaryotic expression plasmid pSectag2b. We conducted an immunogenicity study using C57BL/6J mice, comparing the T-cell responses between the relMtbvs. MIP-3α/relMtb DNA intramuscular vaccination groups.ResultsIntramuscular administration of the DNA vaccine expressing the MIP-3α/relMtb gene fusion induced increased production of various Mtb-protective cytokines (IL-17α, IL-2, TNF-α, IFN-γ) in various mouse tissues, including the spleen, draining lymph nodes and peripheral blood mononuclear cells, relative to the vaccine expressing relMtb alone.ConclusionIntramuscular immunization with a DNA vaccine expressing relMtb/MIP-3α induces robust in vivo Mtb-protective immune signatures, suggesting this may be a promising adjunctive approach in combination with standard anti-TB therapy.Disclosures All Authors: No reported disclosures

Announcement of the 2022 winners of the Spychala and Women in Science Awards

Announcement of the 2022 winners of the Spychala and Women in Science Awards

MiR-199a-3p may be an early warning marker for acute rejection after liver transplantation in rats.

Prevention of acute rejection is the key of the success of liver transplantation. However, there are no specific indicators available for prediction of acute rejection after liver transplantation. MicroRNAs (miRNAs) are highly conserved and small noncoding RNA molecules that can be detected in peripheral blood. Here, we evaluated the potential of circulating miRNAs to serve as noninvasive biomarkers for acute rejection after liver transplantation in rats. The liver grafts retrieved from Lewis rats were orthotopically transplanted into BN rats or Lewis rats in the acute rejection and immune tolerance group respectively, and the BN rats in the immune intervention group was intraperitoneally injected with transforming growth factor-β1 overexpressed immature dendritic cells to suppress acute rejection before orthotopically transplanted with livers from Lewis rats. MiRNAs profiling studies were used to determine the regulation of circulating miRNAs in plasma samples of rats. Candidate miRNA was verified by quantitative reverse transcriptase polymerase chain reaction. Furthermore, the relationship between candidate miRNA and acute rejection was also evaluated. Microarray analysis revealed that miR-199a-3p was the mostly differentially regulated miRNAs in plasma samples among the three groups. The plasmid PCDH-CMV-EGFP-hTGF-β1 was identified by PCR and DNA sequencing, and successfully expressed in imDCs. There were differences in the expression of miR-199a-3p in the liver tissues of the AR group on the 3rd, 7th and 10th day after liver transplantation (all p<0.01). With time, the RAI score increased gradually, and the difference of miR-199a-3p expression gradually increased (rs=0.92, p<0.001), suggesting that it may be related to acute rejection. The expression of miR-199a-3p in the serum of the AR and TGF-β1-imDCs groups gradually increased, reaching a peak at day 7 and then decreasing. There was positive relationship between the expression of miR-199a-3p and RAIs within 7days post operation. (rs=0.942, p<0.05). miR-199a-3p might be an early warning marker for acute rejection after liver transplantation in rats.

Dendritic Cell Migration Is Tuned by Mechanical Stiffness of the Confining Space.

The coordination of cell migration of immune cells is a critical aspect of the immune response to pathogens. Dendritic cells (DCs), the sentinels of the immune system, are exposed to complex tissue microenvironments with a wide range of stiffnesses. Recent studies have revealed the importance of mechanical cues in immune cell trafficking in confined 3D environments. However, the mechanism by which stiffness modulates the intrinsic motility of immature DCs remains poorly understood. Here, immature DCs were found to navigate confined spaces in a rapid and persistent manner, surveying a wide range when covered with compliant gels mimicking soft tissues. However, the speed and persistence time of random motility were both decreased by confinement in gels with higher stiffness, mimicking skin or diseased, fibrotic tissue. The impact of stiffness of surrounding tissue is crucial because most in vitro studies to date have been based on cellular locomotion when confined by microfabricated polydimethylsiloxane structures. Our study provides evidence for a role for environmental mechanical stiffness in the surveillance strategy of immature DCs in tissues.

A DNA Topoisomerase II Inhibitor Results in Ex Vivo Differentiation of THP-1 Cells and Activation of Dendritic Cells.

Effective ex vivo maturation of dendritic cells (DCs) can increase the efficiency of cancer immunotherapy. We aimed to identify novel chemicals with the potential to differentiate and activate immature DCs (iDCs) to mature DCs (mDCs). The expression of surface markers on THP-1 monocytes treated with the screened compounds was analyzed using FACS. Subsequent DC subset analysis and secreted cytokine profiling were also performed. FACS analysis showed that THP-1 cells treated with amsacrine hydrochloride, a DNA topoisomerase II inhibitor, exhibited the typical phenotype of conventional DCs (cDCs). The expression of DC activation markers was also increased after amsacrine treatment. The profile of cytokines produced by THP-1 cells treated with amsacrine was similar to that of mDCs. Amsacrine has an ex vivo capability of differentiating THP-1 monocytes into cDCs. As amsacrine has been used as a stable chemotherapeutic agent in humans, it can be useful for producing mDCs for cancer immunotherapy.

Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells.

The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs). Our study suggests that inhibition of OGT modulates AKT and MEK/ERK pathways in moDCs. Changes were also observed in the expression levels of relevant surface markers, where reduced expression of CD80 and DC-SIGN, and increased expression of CD14, CD86 and HLA-DR occurred. We also noticed decreased IL-10 and increased IL-6 production, along with diminished endocytotic capacity of the cells, indicating that inhibition of O-GlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14medDC-SIGNlowHLA-DRmedCD80lowCD86high profile was noticed when OGT inhibitor, OSMI-1, was present. To evaluate DCs ability to influence T cell differentiation and polarization, we co-cultured these cells. Surprisingly, the observed phenotypic changes of mature moDCs generated in the presence of OSMI-1 led to an increased proliferation of allogeneic T cells, while their polarization was not affected. Taken together, we confirm that shifting the O-GlcNAcylation status due to OGT inhibition alters the differentiation and function of moDCs in in vitro conditions.

Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.