Number Of Langerhans Cells Research Articles

509 Decline in Langerhans cell precursor recruitment into the human skin explains the reduction in epidermal Langerhans cells with age

Aging is accompanied by immunosenescence and increased susceptibility to bacterial and viral infections. Skin provides the first line of physical and immunological defense against environmental insults. However, the age-related changes in the immune function of the human skin are unclear. Here,we investigated the age-related changes in epidermal Langerhans cells (LCs), which play a sentinel role in the initiation of the immune responses in the skin. We screened over 400 normal human skin samples to identify cohorts of young and old sun-protected skin from the same anatomical site. There was a significant reduction in the number of epidermal LCs with age. Among the possible explanations for this reduction, we found a significant reduction in the number of CD14+ CD207+ CCR6+dermal LC precursors with age. In addition, the expression of LC precursor-recruiting chemokine, CXCL14, was markedly down-regulated in the basal layer keratinocytes of the old skin. Importantly, we discovered that young skin recruited more LC precursor-like THP1 cells compared to old skin ex vivo, and this recruitment was inhibited by blocking CXCL14 signaling.Overall, our findings demonstrate an age-related decline in CXCL14-LC precursor axis, which results in the reduction of epidermal LCs under steady-state condition. CXCL14 may provide a novel therapeutic target for prevention of age-related LC reduction.

Qualitative and quantitative study of immune cells in various types of cutaneous lichen planus

Background: Lichen planus (LP) is a common inflammatory skin disease. Pathogenesis of LP includes two possible mechanisms; related or unrelated to antigen. Regarding different clinical features of cutaneous and mucosal types of LP, for the first time, we decided to perform a qualitative and quantitative study of immune cells in different types of cutaneous LP and in comparison with normal skin. Methods: A total of 88 specimens (60 cases of cutaneous LP, 28 cases of normal skin) were selected from 2016 to 2017 in Kerman, Iran. Evaluation of immune cells was carried out based on qualitative and quantitative analysis. These findings were statistically calculated by descriptive statistical tests including frequency and mean ± standard deviation. Quantitative data were analyzed by independent t-test, chi-square, and analysis of variance (ANOVA). Data were analyzed using SPSS16 (SPSS Inc., Chicago, IL, USA). A p value less than 0.05 was considered statistically significant. Results: Our study demonstrated that the mean number of immune cells was significantly higher in lichen planus group in comparison with the control group. Number and staining intensity of Langerhans cells (LCs) in the LP group were significantly greater in epidermal than dermal region. Mastocytes were located mostly within the deep dermis in the LP group. Hypertrophic and atrophic LP had the highest and the lowest number of immune cells (i.e., mastocytes, LCs, and CD3 positive cells), respectively, with a significant difference. Conclusion: Our study demonstrated that immune cells were seen in larger numbers in the hypertrophic type of cutaneous LP which is consistent with the chronicity of this disease.

Results of laser confocal microscopy of the cornea in viral uveitis (a preliminary report)

To evaluate the results of laser corneal confocal microscopy (CCM) in viral uveitis of varying localization. The main study group included 23 patients (23 eyes) diagnosed with unilateral herpesviral uveitis (chorioretinitis), the patients' age varied from 18 to 79 years. The control group comprised 19 healthy volunteers (38 eyes) aged 20 to 75 years. In addition, the paired eyes of the main group patients were examined. In all patients, standard ophthalmologic examination was complemented with CCM performed on the HRT III device with a corneal module, followed by analysis of the course and structure of corneal nerve fibers (CNF) using copyrighted software Liner 1.2. The preliminary results achieved in this study outline the prospects for further research on the state of cornea (in particular, changes in the course and structure of CNF, and the presence of dendritiform cells of Langerhans) with laser CCM in patients with uveitis of various etiologies. These morphological changes also has potential use as diagnostic markers of inflammation of the uveal tract. The main criteria for assessing the state of cornea in viral uveitis include the following: increased tortuosity of CNF, increase in the number and size of Langerhans cells. Further research - in particular, studying the integrated use of diagnostic methods necessary for the verification of viral uveitis, as well as detailed analysis of the history and clinical picture of the disease - is required to substantiate the inclusion of laser confocal microscopy method in the algorithm for the diagnosis of viral uveitis.

In situ immune response in human dermatophytosis: possible role of Langerhans cells (CD1a+) as a risk factor for dermatophyte infection.

ABSTRACTDermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis.

In Vivo Confocal Microscopy Analysis of the Corneal Layers in Adenoviral Epidemic Keratoconjunctivitis

Objectives:To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy (IVCM) in patients with adenoviral epidemic keratoconjunctivitis (EKC).Materials and Methods:The study included 20 eyes of 12 patients who presented to the Kocaeli University Medical Faculty, Department of Ophthalmology with complaints of watering, crusting, and stinging, were clinically diagnosed EKC, and were examined by slit-lamp biomicroscopy and IVCM during the prodromal phase and the punctate keratitis, deep epithelial keratitis, and subepithelial infiltration stages of EKC.Results:While biomicroscopic examination findings were normal during the prodromal period of EKC, IVCM showed an increase in Langerhans cell numbers in the subbasal plexus. After onset of clinical EKC, the punctate epithelial keratitis stage was characterized by findings of hyperreflective cell clusters in the basal epithelium layer, increased accumulation of Langerhans cells in Bowman’s layer, and hyperreflectivity in the anterior stromal layers. In the deep epithelial keratitis stage, the basal epithelial cells displayed peripheral hyperreflectivity and the hyperreflectivity of the anterior stromal surface increased and became more rounded. In the subepithelial keratitis stage, these findings persisted in addition to increased anterior stromal surface hyperreflectivity and focal round plaques.Conclusion:This study shows that the inflammatory process in the cornea starts in the prodromal period of EKC. Massive inflammation of the epithelium and stroma was observed in the active phase and focal changes were observed on the anterior stromal surface starting in the subepithelial infiltration period.

Stat3 activation in epidermal keratinocytes induces Langerhans cell activation to form an essential circuit for psoriasis via IL-23 production

BackgroundPsoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial. ObjectivesTo elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model. MethodsTwo lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer. ResultsLCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasis patients produced IL-23. ConclusionsOur study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.

Immunological dysfunction in chronic arsenic exposure: From subclinical condition to skin cancer.

Exposure to arsenic is a global health issue. Long-term arsenic exposure may associate with various cancers and many other pathological effects. Over 100 million people worldwide are exposed to arsenic particularly in countries such as Bangladesh, Chile, China, India, Mexico, Taiwan and the USA. Drinking of water contaminated with arsenic is the major route of human exposure. Skin lesions are considered to be the most common adverse effects associated with chronic arsenic exposure. Skin lesions usually develop with the latency period spanning more than 20 years from first exposure. Arsenic-induced Bowen's disease, the most frequently encountered carcinoma in situ resulting from chronic arsenic exposure, is characterized by multiple and recrudescent lesions. Long-term arsenic exposure results in impaired immunity in susceptible individuals. In the prenatal stage, enhanced placental inflammatory responses and reduced placental T cells by arsenic may result in decreased thymic size and functions in newborns. In childhood, arsenic exposure may reduce peripheral CD4+ cells and interleukin-2 secretion which leads to susceptibility to opportunistic infections. There was an impairment of macrophage function and oxidative DNA damage of peripheral polymorphonuclear leukocytes in adults with skin lesions. In arsenic-induced Bowen's disease lesions, a decrease in the number and functions of Langerhans cells and, in parallel, a selective CD4+ cell apoptosis was noticed. These findings provide scientific evidence for understanding the phenomenon of arsenic-induced immune escape in the early stage of carcinogenesis and a reasonable explanation for multiple and recrudescent arsenic cancers in the skin.

TGF-β1 regulates epidermal LCs in a Smad-independent pathway

Abstract Transforming growth factor-β1 (TGF-β1) is a key factor for Langerhans cell (LC) homeostasis and maintaining in the epidermis, but the underlying mechanisms in TGF-β signaling pathways remain elusive. Canonically, binding of TGF-β to TGF-βR activates Smad2 or Smad3, which subsequently heterodimerizes with Smad4 and then translocates into the nucleus acting as transcriptional regulators of TGF-β1 target genes. In order to investigate if Smad-dependent pathways are required for epidermal LC maintenance, we first crossed CSF1R-Cre and hLangerin-Cre transgenic mice with Smad2fl/fl and Smad4fl/fl, mice to generate the mutant mice with conditional Smad2 and Smad4 deletion at birth (CSF1Rcre) or 3 days after birth (hlangerinCre). Surprisingly, deletion of individual Smad2 or Smad4 in LCs did not significantly affect their ratios in skin and their expression of MHC-II, CD80 and CD86 in both models. The phagocytic capacity of LCs from KO mice was unaltered in vivo and in vitro compared to WT LCs. Furthermore, upon in vitro stimulation, MHC-II, CD80 and CD86 were comparably unregulated on LCs between KO and WT mice. We further tested LC number and maturation in conventional Smad3KO mice as well as Smad2/4 double KO mice induced by CSF1Rcre, the number and maturation of LCs are comparable between mutant and WT mice. Overall, our data suggest that conventional TGF-β/Smad2/3/4 signaling pathways may not be required for maintaining LC homeostasis and immature stage in the epidermis and LC maturation upon stimulation. The underlying mechanisms that Smad2/3/4-independent TGF-β pathways involved in LC maintenance and function remain to be further determined.

Immunohistochemical Analysis of S100-Positive Langerhans Cells in the Healthy Gingiva and Periodontal Disease

Langerhans cells are antigen presenting cells, located in the stratified squamous epithelium of the skin and oral epithelium. A high density of Langerhans cells in gingival epithelium associated with an inflammatory process has been demonstrated in the literature by numerous studies, although the relationship with inflammation was less investigated.The aim of our study was to evaluate the distribution, density, morphology of Langerhans cells in both gingival epithelium and the associated inflammatory infiltrate in the lamina propria of the gingiva. The relationship between Langerhans cells and inflamatory process was also assesed. The present study included a number of 51 gingival biopsies. 12 of these didn� t show significant changes on routine examination. In all of the other 39 cases the presence of inflammatory lesions was noticed. The inflamatory infiltrate was described by using hematoxylin eosin staining and quantitative score, with values between 0 and 3. Langerhans cells were immunohistochemicaly highlighted by using S100 antibody and quantified with hot spot method.We found an increase of Langerhans cells density in all cases of inflammation as compared with healthy gingival tissue. The highest density was found in the 13 cases with severe inflammation. At these last cases was noticed a migration tendency of Langerhans cells from infiltrate inflamatory area to basal layer of the epithelium. The results of this study indicated that Langerhans cells number is higher in inflamatory gingival tissue comparative with normal tissue, and the density of these cells is in relation with the severity of the inflammatory process.

A pilot study on corneal Langerhans cells in keratoconus.

To report the density and morphology of cells that are analogous to corneal Langerhans cells and their associations in keratoconus. This prospective cross-sectional study included a convenience sample of keratoconus subjects aged between 18-65 years. Corneal topography, assessment of ocular symptoms, tear variables, corneal sensitivity, in-vivo confocal microscopy were performed. The number of Langerhans cells were manually counted and averaged across three central corneal images. Cell morphology was graded on a 0-3 scale, where grade 3 indicates cells with long visible dendrites. Associations of Langerhans cells with other variables were evaluated using Spearman's correlation. Twenty-one keratoconus subjects with a mean age of 43±11 years were included. Eighty-one percent of them were males, 48% had mild keratoconus and 52% were contact lens wearers. Langerhans cells were present in the central cornea in 91% of subjects. Median cell density was 15 cells/mm2(IQR: 3-21). Cell morphology of grades 2 or 3 (with short or long dendrites) was seen in 71% of subjects. There was a significant association between Langerhans cell frequency and density with male gender (rho and p-values: -0.669, 0.001 and -0.441,0.045) and between Langerhans cell density and nerve fibre tortuosity (0.479,0.028). No significant association observed with age, contact lens wear or ocular symptoms. Langerhans cells were present in a significant number of subjects suggesting the possibility of inflammation in keratoconus. Based on the association of Langerhans cells with nerve parameters, we propose inflammation as the underlying cause for corneal nerve changes in keratoconus.

416 No difference in UVB induced changes in antigen presenting cells and cytokines between subjects with and without FLG null-mutation

Epidermal filaggrin deficiency may affect UVB induced immune responses. We examined if common filaggrin gene (FLG) null-mutations were associated with altered responses in antigen presenting cells and cytokines following UVB irradiation of human skin in vivo. Atopic heterozygotic FLG null-mutation carriers and healthy wildtype subjects(WT) were included. Skin on the volar forearm was irradiated with 1.5 minimal erythema dose UVB. Suction blisters were raised on skin irradiated 24 and 72 hours earlier and on non-irradiated control skin(C). Antigen presenting cell numbers and activation markers were examined in epidermal single cell suspensions by flow cytometry. Concentrations of IL-1β, IL-6, IL-10, IL-12p70, TNF-α, TGF-β1, and CCL20 were measured in blister fluid. As expected, UVB irradiation caused a significant decrease in Langerhans cell (LC) numbers, a significant increase in monocyte numbers, and a significant upregulation of activation markers CD86 and OX40 ligand on LCs. These changes did not differ between heterozygotic and WT subjects: deltaLC 24hrs - C; P=0.44, deltaLC 72hrs - C; P=0.20, deltaMonocytes 24hrs - C; P=0.19, deltaMonocytes 72hrs - C; P=0.38, deltaCD86 24hrs - C; P=0.38, deltaCD86 72hrs - C; P=0.10, deltaOX40L 24hrs - C; P=0.28, deltaOX40L 72hrs - C; P=0.51(N=8+8). UVB irradiation upregulated IL-1β, IL-6, and TGF-β1, but these changes were not influenced by FLG mutation status either: deltaIL-1β 24hrs - C; P=0.84(N=5+6), deltaIL-1β 72hrs - C; P>0.99(N=5+6), deltaIL-6 24hrs - C; P=0.91(N=5+6), deltaIL-6 72hrs - C; P=0.91(N=5+6), deltaTGF-β1 24hrs - C; P=0.96(N=5+7), deltaTGF-β1 72hrs - C; P=0.43(N=5+7). Taken together, we found no difference in changes of antigen presenting cells and cytokines in UVB irradiated skin from subjects with and without a FLG null-mutation.

627 A single sunburn influences the immune component of human skin for up to 14 days

Sunburn is prevalent and while the clinical effects disappear quickly, repeated episodes have long term consequences such as skin cancer. Pro-inflammatory eicosanoid expression and leukocyte infiltration characterise the peak of the sunburn response, however, little is known of these processes during the resolution phase. We examined changes in eicosanoid expression and leukocyte infiltration up to 14 days post acute sunburn. Photoprotected buttock skin was exposed to 3xMED of broadband UVR and skin erythema measured over 14 days (n=13; 20-58yrs, 8F, phototype I-III). Biopsies and suction blister fluid were sampled from unexposed and UVR-exposed skin over the 14 day time-course and analysed by immunohistochemistry (neutrophil elastase, CD4, CD8, CD68, CD1a, COX-2, EP4) and LC-MS/MS (eicosanoids). Erythema, COX-2, eicosanoid production and infiltration of innate immune cells (neutrophils and macrophage), peaked at D1 post UVR. By D7 erythema showed 60% resolution, while expression of the prostaglandin E2 receptor EP4 remained elevated at D14. Infiltration of adaptive immune cells (CD4+, CD8+ T cells) peaked at D4-D7 and remained above baseline at D14 (p<0.01, p<0.001 respectively). Moreover, the CD4+:CD8+ ratio rose post-UVR, peaking at 4.3:1 at D1, compared with 2:1 at D0. In contrast, epidermal Langerhans cell numbers showed maximum reduction (∼50%) at D4-D7 (p<0.01), only fully returning to baseline at D14. Acute UVR exposure has profoundly impacts epidermal antigen presenting cell number persisting for up to 2 weeks following the initial insult. Thus a single sunburn may trigger a prolonged immunosuppressive environment compromising ability to respond to neoplastic change and exogeneous challenge.

Rats bred for low and high running capacity display alterations in peripheral tissues and nerves relevant to neuropathy and pain.

IntroductionDiet and activity are recognized as modulators of nervous system disease, including pain. Studies of exercise consistently reveal a benefit on pain. This study focused on female rats to understand differences related to metabolic status and peripheral nerve function in females.MethodsHere, we investigated parameters of peripheral nerve function relevant to pain in rats selectively bred for high (high‐capacity runners; HCR) or low endurance exercise capacity (low‐capacity runners; LCR) resulting in divergent intrinsic aerobic capacities and susceptibility for metabolic conditions.Results LCR female rats have reduced mechanical sensitivity, higher intraepidermal nerve fiber density and TrkA‐positive epidermal axons, increased numbers of Langerhans and mast cells in cutaneous tissues, and a higher fat content despite similar overall body weights compared to female HCR rats. Sensory and motor nerve conduction velocities, thermal sensitivity, and mRNA expression of selected genes relevant to peripheral sensation were not different.ConclusionsThese results suggest that aerobic capacity and metabolic status influence sensory sensitivity and aspects of inflammation in peripheral tissues that could lead to poor responses to tissue damage and painful stimuli. The LCR and HCR rats should prove useful as models to assess how the metabolic status impacts pain.

Significant association of inflammation grade with the number of Langerhans cells in odontogenic keratocysts.

Langerhans cells (LCs) are antigen-presenting cells. This study assessed the LC counts in odontogenic keratocysts (OKCs). The LC numbers in the lining epithelia and subepithelial connective tissues were counted at 60 OKC sites without inflammation, 39 OKC sites with mild/moderate inflammation, and 13 OKC sites with severe inflammation from 60 OKC specimens immunostained with anti-S100 antibodies. The mean LC counts in the lining epithelia and subepithelial connective tissues increased significantly from no inflammation (0.5±0.4 and 0.7±0.6 cell/high-power field or HPF, respectively) through mild/moderate inflammation (5.9±2.7 and 5.0±3.5 cells/HPF, respectively) to severe inflammation OKC sites (14.7±5.3 and 13.3±6.8 cells/HPF, respectively; all P-values<0.001). OKC sites with inflammation had thicker lining epithelia than those without inflammation. Moreover, the mean LC counts in the lining epithelia and subepithelial connective tissues of OKCs were significantly higher in the thicker lining epithelium (>100μm) group (7.7±5.6 and 6.5±5.8 cells/HPF, respectively) than in the thinner lining epithelium (≦ 100μm) group (1.0±2.0 and 1.4±2.6 cells/HPF, respectively; both P-values<0.001). A significant association of inflammation grade with the number of LCs in OKCs is found. The paucity of finding LCs in the lining epithelia of OKCs without inflammation indicates the loss of immunosurveillance ability against the OKC lining epithelial cells; this can explain why OKCs have aggressive clinical behavior, a great growth potential, and a high recurrence rate.

Significant association of high-grade inflammation and thick lining epithelium with the increased number of Langerhans cells in dentigerous cysts.

Langerhans cells (LCs) are antigen-presenting cells. This study assessed the LC counts in 80 dentigerous cysts (DCs). The CD1a-positive LC numbers in the lining epithelia and subepithelial connective tissues were counted at 80 DC sites without inflammation, 33 DC sites with mild/moderate inflammation, and 9 DC sites with severe inflammation from 80 DC specimens. The mean LC counts in the lining epithelia and subepithelial connective tissues increased significantly from no inflammation (0.5±0.5 and 0.2±0.3cell/high-power field or HPF, respectively) through mild/moderate inflammation (6.8±1.8 and 2.4±2.0cells/HPF, respectively) to severe inflammation DC sites (18.9±7.0 and 6.7±5.8cells/HPF, respectively; all P-values<0.001). DC sites with inflammation had thicker lining epithelia than those without inflammation. Moreover, the mean LC counts in the lining epithelia and subepithelial connective tissues of DCs were significantly higher in the thicker lining epithelium (>50μm) group (7.4±6.5 and 2.6±3.4cells/HPF, respectively) than in the thinner lining epithelium (≦ 50μm) group (0.5±0.5 and 0.2±0.3cells/HPF, respectively; both P-values<0.001). A significant association of high-grade inflammation and thick lining epithelium with the increased LC number in DCs is found. The finding of few LCs in the lining epithelia of DCs without inflammation indicates the reduced immunosurveillance ability against DC lining epithelial cells in DC patients. It needs further studies to confirm the role of reduced immunosurveillance in the enlargement of the DC.

Corneal Subbasal Nerve Analysis Using In Vivo Confocal Microscopy in Patients With Dry Eye: Analysis and Clinical Correlations.

This study aimed to observe corneal subbasal nerves and Langerhans cells (LCs) using in vivo confocal microscopy (IVCM) in patients with dry eye, a tool for the evaluation of disease stage and severity and for treatment monitoring at the microstructural level. A total of 107 eyes from 62 patients were included. The Ocular Surface Disease Index (OSDI) questionnaire and other examinations were used to assess dry eye symptoms and signs. IVCM was performed to observe subbasal corneal nerves and LCs. Corneal nerves were graded using both objective and subjective methods. The correlations between dry eye symptoms and corneal nerve parameters, corneal nerve grading, and LC number were analyzed. Corneal nerve length was negatively correlated with sensitivity to light [correlation coefficient (CC)= -0.24, P < 0.05]; nerve width was positively correlated with the OSDI score, painful eyes, and blurred vision (CC = 0.41, 0.23, and 0.46, respectively, all P < 0.05); and nerve tortuosity was positively correlated with sensitivity to light (CC = 0.23, P < 0.05). Moreover, both total objective and subjective grading scores were positively correlated with OSDI scores (CC = 0.48 and 0.27, respectively, both P < 0.05). LC number was found not to be significantly correlated with dry eye symptoms (P > 0.05). IVCM is a useful tool to evaluate corneal subbasal nerve changes in patients with dry eye. Detailed nerve grading could help to understand and evaluate the pathophysiologic conditions of the disease and could be used for further treatment follow-up in the future.

Geographic tongue: assessment of peripheral nerve status, Langerhans cell, and HLA-DR expression

The objectives of this study were to determine whether geographic tongue (GT) is an antigen-driven condition by assessing Langerhans cell numbers and the expression of human leukocyte antigen (HLA)-DP, -DQ, and -DR in the epithelium of GT and to assess peripheral nerve status for any possible damage/injury association by quantifying neurite area in connective tissue in GT. Randomly selected samples of GT were examined by using routine immunoperoxidase staining methods to S100 protein, neurofilament, CD1a, and HLA class II. The Student t test and Mann-Whitney U test were used to assess statistical significance. Langerhans cell numbers were found to be increased in GT. HLA expression was also seen in Langerhans cells and inflammatory cells and in the spinous layer and parabasal epithelial cells in 2 samples of GT. Total nerve tissue, based on area measurements, was not significantly different between GT and control tissues. The increase in Langerhans cells suggests that GT is a condition that is likely driven by an unknown external antigen. Peripheral nerve damage was not apparent, suggesting that this is not a mechanism whereby patients with GT become symptomatic.

Depletion of Epidermal Langerhans Cells in the Skin Lesions of Pellagra Patients.

Pellagra is a nutrient deficiency disease caused by insufficient niacin levels. Recent studies have shown that numbers of epidermal Langerhans cells decreased in other diseases caused by nutritional deficiencies, including necrolytic migratory erythema and acrodermatitis enteropathica. Epidermal Langerhans cells are capable of modulating or even halting the inflammatory reaction. The aim of this study was to examine changes in the number of Langerhans cells and other dendritic cells, and maturation of epidermal Langerhans cells in the lesional and adjacent non-lesional skin in pellagra patients. Seven pellagra patients and 10 healthy individuals who served as controls were included. The number and distribution of dendritic cells and other cutaneous cells were examined by immunohistochemistry. Epidermal Langerhans cells decreased considerably in the skin lesions of pellagra patients, whereas other dendritic cells did not change. The decrease in the number of Langerhans cells was positively correlated with the histological severity of skin lesions. As the number of Langerhans cells was not reduced in the undisturbed neighboring skin, the depletion of epidermal Langerhans cells did not precede skin damage but was a cause of prolonged severe inflammation.

Immunohistopathology of the Newly Discovered Giant Papillae Tongue Disorder in Organ-Transplanted Children.

Giant papillae tongue disorder (GPTD) is a newly discovered, long-lasting clinical disorder that may develop in organ-transplanted pediatric recipients. The key feature of this disorder is the unique tongue lesion, which comprises swollen fungiform papillae. The aim of this study was to characterize the immunohistopathology of this novel inflammatory condition. Six organ transplanted children with GPTD were included in the study. Routine histopathology and immunohistochemical stainings for CD3, CD4, CD8, CD25, FOXP3, CD20, CD138, CD68, CD1a, CD15, CD23, and mast cell tryptase were performed. Immunohistochemical analyses of the oral lesions revealed a subepithelial infiltrate that was primarily composed of CD3- and CD4-positive T cells, CD20-expressing B cells, macrophages, and CD138-positive plasma cells. The CD20-positive cells did not display the typical B cell morphology, having in general a more dendritic cell-like appearance. The CD138-expressing plasma cells were distinctly localized as a dense infiltrate beneath the accumulation of T cells and B cells. Increased numbers of CD1a-expressing Langerhans cells were detected both in the epithelium and connective tissue. Because no granulomas were observed and only single lesional eosinophils were detected, GPTD does not resemble a granulomatous or eosinophilic condition. We describe for the first time the immunopathological characteristics of a novel inflammatory disorder of the oral cavity, which may develop after solid organ transplantation in children.

Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment

BackroundIn vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three‐month treatment with autologous serum eye‐drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy.MethodsTwenty‐six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three‐month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub‐basal nerve plexus fibres were evaluated.ResultsA significant decrease in corneal fluorescein staining was found after the three‐month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres.ConclusionsThe results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow‐up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients.