Morphology Of Langerhans Cells Research Articles

Influence of E-cadherin deficiency on the dendrite morphology of Langerhans cells.

The expression of E-cadherin on Langerhans cells (LC) is required for adequate dendrite intercalation between epidermal keratinocytes. Upon disruption of epidermal homeostasis by tape stripping, E-cadherin competent LC extend dendrites reaching up to the epidermal surface, while E-cad deficient LC lack this ability.

Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion.

Our objective in this study was to analyze the aberrant neural regeneration activity in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus patients and 29 age-matched healthy control subjects. Corneal nerve fiber density (CNFD, the number of fibers/mm2) and peripheral Langerhans cell morphology were lower (p < 0.05) in systemic lupus erythematosus patients compared to the control group. Interestingly, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber total branch density, and corneal nerve fiber area showed a negative correlation with disease duration. A negative correlation was also demonstrated between average corneal nerve fiber density and central Langerhans cell density. This is in line with our hypothesis that corneal somatosensory terminal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk not only disrupts regeneration and keeps transcription activated, but could lead to Piezo1 downregulation and cell activation on Langerhans cells when we consider a chronic path. Hence, Piezo2 containing mechanosensory corneal nerves and dendritic Langerhans cells could also be regarded as central players in shaping the ocular surface neuroimmune homeostasis through the Piezo system. Moreover, lost autoimmune neuroinflammation compensation, lost phagocytic self-eating capacity, and lost transcription regulation, not to mention autoantibodies against vascular heparin sulfate proteoglycans and phospholipids, could all contribute to the progressive fashion of dry eye disease in systemic lupus erythematosus.

Immunolocalization of CD1a expressing dendritic cells in sinonasal polyposis

ABSTRACT Sinonasal polyps are benign projections of edematous nasal mucosa lined by respiratory epithelium. Langerhans cells (LCs) belonging to the dendritic cell family located in respiratory epithelium are involved in antigen presentation and maintenance of local immunological homeostasis. This study aims to elucidate the morphology and distribution of CD1a positive LCs in normal nasal mucosa and compare the same with polypoid nasal mucosa by immunohistochemistry. Normal nasal mucosa (n = 20) was obtained from patients who underwent septoplasty for deviated nasal septum. Polypoid nasal mucosa (n = 22) was obtained from patients with chronic rhinosinusitis (CRS) or allergic fungal rhinosinusitis who underwent excision of nasal polyps. The tissues obtained were processed for immunohistochemistry and stained with CD1a-EP80 Rabbit monoclonal antibody. In the tissues studied, CD1a positive LCs were observed in both the epithelium and lamina propria. Different morphological subtypes of LCs were noted in the epithelium. The cells were distributed adjacent to walls of subepithelial capillaries and cysts. The median number of CD1a positive LCs was significantly higher in polypoid category (13.5 per mm2) as compared with normal nasal mucosa (2.5per mm2) (p = .001). Presence of CD1a positive LCs in polypoid nasal mucosa hints at a critical immunological role in the etiopathogenesis of nasal polyps.

Aspects of Langerhans cells and TNF-α in the cutaneous immunity of anogenital warts

BackgroundAnogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α. ObjectiveTo assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented. MethodsThis is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium. Results48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p<0.001). Study limitationsSmall number of patients analyzed. ConclusionThere was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.

Langerhans cells in hypospadias: an analysis of Langerin (CD207) and HLA-DR on epidermal sheets and full thickness skin sections

BackgroundHypospadias are among the most common genital malformations. Langerhans Cells (LCs) play a pivotal role in HIV and HPV infection. The migration of LC precursors to skin coincides with the embryonic period of hypospadias development and genetic alterations leading to the formation of hypospadias impact the development of ectodermally derived tissues. We hypothesized that this might be associated with a difference in frequency or morphology of epidermal and dermal LCs in hypospadias patients.MethodsA total of 43 patients from two centers were prospectively included into this study after parental consent and ethics approval. Epidermal and dermal sheets were prepared from skin samples of 26 patients with hypospadias, 13 patients without penile malformations and 4 patients with penile malformations other than hypospadias. Immunofluorescence staining of sheets was performed with anti-HLA-DR-FITC and anti-CD207/Langerin-A594 antibodies. Skin sections from 11 patients without penile malformation and 11 patients with hypospadias were stained for Langerin. Frequencies as well as morphology and distribution of epidermal and dermal LCs on sheets and sections were microscopically evaluated. Cell counts were compared by unpaired t-tests.ResultsThere was no difference in frequency of epidermal LCs, Neither on sheets (873 ± 61 vs. 940 ± 84LCs/mm2, p = 0.522) nor on sections (32 ± 3 vs. 30 ± 2LCs/mm2, p = 0.697). Likewise, the frequency of dermal LCs (5,9 ± 0,9 vs. 7.5 ± 1.3LCs/mm2, p = 0.329) was comparable between patients with hypospadias and without penile malformation. No differences became apparent in subgroup analyses, comparing distal to proximal hypospadias (p = 0.949), younger and older boys (p = 0.818) or considering topical dihydrotestosterone treatment prior to surgery (p = 0.08). The morphology of the LCs was not different comparing hypospadias patients with boys without penile malformations.ConclusionsLCs are present in similar frequencies and with a comparable morphology and distribution in patients with hypospadias as compared to children without penile malformations. This suggests that patients with hypospadias are not different from patients with normal penile development considering this particular compartment of their skin immunity.

Antidiabetic effect of withanolides and liraglutide on serum insulin level and pancreatic histology in diabetic rats.

Objectives: Type 2 diabetes is characterized by hyperglycemia and occurs as a result of insulin resistance and pancreatic beta cells failure to compensate. Present study was conducted to determine the antidiabetic effect of Withania coagulans and liraglutide on postprandial serum insulin levels and pancreatic histological features in streptozotocin induced diabetic rat. Study Design: This Randomized Control Trial. Setting: At multidisciplinary lab Islamic International Medical College, Rawalpindi in collaboration with Animal House, National Institute of Health, Islamabad. Period: From March 2016 to April 2017. Material and Methods: Forty male Sprague daily rats were randomly divided into normal Control Group A (n=10) and Experimental Group (n=30). Experimental group was given streptozotocin (30mg/kg/day) intraperitoneally for 5 days and diabetes was confirmed in experimental group by measuring fasting blood glucose level (mg/dl). Experimental group was divided further into Group B (Diabetic control), Group C (Withania coagulans treated) and Group D (Liraglutide treated). Group C were given Withania coagulans in addition to normal diet and Group D received Liraglutide besides normal diet for 30 days. Second sampling for evaluating postprandial serum insulin level and pancreatic histology was done after 30 days. Result: Postprandial serum insulin levels of Withania coagulans treated Group C (5.54 + 0.23 μU/ml) and Liraglutide treated Group D (6.06 + 0.17 μU/ml) were significantly raised in comparison with Diabetic control Group B (3.50 + 0.19 μU/ml), whereas islets of Langerhans cell morphology were markedly improved in Group C and D as compared to Group B. Conclusion: Withania coagulans significantly increases postprandial serum insulin level and improves pancreatic beta cells architecture.

Supramolecular Modification of ABC Triblock Terpolymers in Confinement Assembly.

The self-assembly of AB diblock copolymers in three-dimensional (3D) soft confinement of nanoemulsions has recently become an attractive bottom up route to prepare colloids with controlled inner morphologies. In that regard, ABC triblock terpolymers show a more complex morphological behavior and could thus give access to extensive libraries of multicompartment microparticles. However, knowledge about their self-assembly in confinement is very limited thus far. Here, we investigated the confinement assembly of polystyrene-block-poly(4-vinylpyridine)-block-poly(tert-butyl methacrylate) (PS-b-P4VP-b-PT or SVT) triblock terpolymers in nanoemulsion droplets. Depending on the block weight fractions, we found spherical microparticles with concentric lamella–sphere (ls) morphology, i.e., PS/PT lamella intercalated with P4VP spheres, or unusual conic microparticles with concentric lamella–cylinder (lc) morphology. We further described how these morphologies can be modified through supramolecular additives, such as hydrogen bond (HB) and halogen bond (XB) donors. We bound donors to the 4VP units and analyzed changes in the morphology depending on the binding strength and the length of the alkyl tail. The interaction with the weaker donors resulted in an increase in volume of the P4VP domains, which depends upon the molar fraction of the added donor. For donors with a high tendency of intermolecular packing, a visible change in the morphology was observed. This ultimately caused a shape change in the microparticle. Knowledge about how to control inner morphologies of multicompartment microparticles could lead to novel carbon supports for catalysis, nanoparticles with unprecedented topologies, and potentially, reversible shape changes by light actuation.

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.

Comparison of global gene expression profiles of microdissected human foetal Leydig cells with their normal and hyperplastic adult equivalents

Do human adult Leydig cells (ALCs) within hyperplastic micronodules display characteristics of foetal LCs (FLCs)? The gene expression profiles of FLCs and all ALC subgroups were clearly different, but there were no significant differences in expressed genes between the normally clustered and hyperplastic ALCs. LCs are the primary androgen producing cells in males throughout development and appear in chronologically distinct populations; FLCs, neonatal LCs and ALCs. ALCs are responsible for progression through puberty and for maintenance of reproductive functions in adulthood. In patients with reproductive problems, such as infertility or testicular cancer, and especially in men with high gonadotrophin levels, LC function is often impaired, and LCs may cluster abnormally into hyperplastic micronodules (defined as clusters of >15 LCs in a cross-section). A genome-wide microarray study of LCs microdissected from human foetal and adult tissue samples (n=12). Additional tissue specimens (n=15) were used for validation of the mRNA expression data at the protein level. Frozen human tissue samples were used for the microarray study, including morphologically normal foetal (gestational week 10-11) testis samples, and adult testis specimens with normal LC distribution, LC micronodules or LC micronodules adjacent to hCG-producing testicular germ cell tumours. Transcriptome profiling was performed on Agilent whole human genome microarray 4×44 K chips. Microarray data pre-processing and statistical analysis were performed using the limma R/Bioconductor package in the R software, and differentially expressed genes were further analysed for gene set enrichment using the DAVID Bioinformatics software. Selected genes were studied at the protein level by immunohistochemistry. The transcriptomes of FLCs and ALCs differed significantly from each other, whereas the profiles of the normally clustered and hyperplastic ALCs were similar despite morphological heterogeneity. The study revealed several genes not known previously to be expressed in LCs during early development, including sulfotransferase family 2A member 1 (SULT2A1), WNT1-inducible signalling pathway protein 2 (WISP2), hydroxyprostaglandin dehydrogenase (HPGD) and insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), whose expression changes were validated at the protein level. The transcriptomic data are deposited in ArrayExpress (accession code E-MTAB-5453). The small number of biological replicates and the necessity of RNA amplification due to the scarcity of human tissues, especially foetal specimens, are the main limitations of the study. Heterogeneous subpopulations of LCs within micronodules were not discriminated during microdissection and might have affected the expression profiling. The study was constrained by the lack of availability of truly normal controls. Testis samples used as 'controls' displayed complete spermatogenesis and were from patients with germ cell neoplasia but with undetectable hCG and normal hormone levels. The changes in LC morphology and function observed in patients with reproductive disorders possibly reflect subtle changes in the expression of many genes rather than regulatory changes of single genes or pathways. The study provides new insights into the development and maturation of human LCs by the identification of a number of potential functional markers for FLC and ALC. The study was supported by research grants from the Danish Cancer Society, the Capital Region's Research Fund for Health Research, Rigshospitalet's research funds, the Villum Kann Rasmussen Foundation, the Danish Innovation Fund, ReproUnion, Kirsten and Freddy Johansen's foundation and the Novo Nordisk Foundation. None of the funding agencies had any influence on the study. The authors declare no conflicts of interest.

Skin aging in patients with acquired immunodeficiency syndrome.

To evaluate the histomorphometric skin changes over aging patients with autopsied acquired immunodeficiency syndrome (AIDS). In 29 skin fragments of autopsied elderly (older than 50 years) and nonelderly patients with AIDS, epidermal thickness, the number of layers, the diameter of cells, the percentage of collagen and elastic fibers in the dermis, and the number and morphology of Langerhans cells were assessed. Statistical analysis was performed by SigmaStat 2.03 program. The thickness of the epidermis (92.55 × 158.94 μm), the number of layers (7 × 9 layers), and the diameter of the cells (13.27 × 17.6 μm) were statistically lower among the elderly. The quantity of collagen fibers (9.68 × 14.11%) and elastic fibers (11.89 × 15.31%) was also significantly lower in the elderly. There was a decrease in total (10.61 × 12.38 cel/mm(2)) and an increase in immature Langerhans cells (6.31 × 4.98 cel/mm(2)) in elderly patients with AIDS. The aging of the skin of patients with AIDS is amended in different histomorphometric aspects, the epidermis constituents suffer less pronounced changes in normal aging, and the dermis has more intense changes in elastic fibers and collagen.

Heptapeptide-loaded solid lipid nanoparticles for cosmetic anti-aging applications

The cosmetic industry requires more and more expensive actives and ingredients such as retinol, coenzyme Q10, proteins, peptides and biotechnologically produced molecules. In this study, we demonstrate the development of a cost effective formulation of a nanostructured lipid carrier (NLC) or solid lipid nanoparticles (SLN) improving peptide delivery into skin. NLC or SLN are very suitable vehicles for the delivery of active ingredients into skin. The SLN, produced by using hot high pressure homogenization method combine advantages such as physical stability, protection of incorporated labile actives and controlled release. By the used method we dispersed the amorphous heptapeptide DEETGEF in shea butter and homogenized this pre-dispersion at 60°C together with the water phase using a Microfluidizer at 1000bar. The analysis of the obtained SLN-P7 showed a particle size of 173nm, incorporated peptide of 0.014%, entrapment efficiency of 90.8%, melting peak (DSC) of the core lipid of 27°C and a zeta potential of −54mV. By an ex vivo study with skin explants we could stimulate NQO1 (NAD(P)H quinone oxidoreductase), HMOX1 (Heme oxygenase-1) and PRDX1 (Peroxiredoxin-1) genes all of which are cell protecting enzymes. In a multicellular protection against UV induced stress study with skin explants we detected the formation of sun burn cells and the number and morphology of Langerhans cells. The application of our SLN-P7 formulation on skin explants led to a significant and dose dependent protection against UV irradiation. In the clinical suction blister study, irradiation with UVA light for two hours after final product application led to a statistically significant increase of the 8-OhdG (8-hydroxy-2′-deoxyguanosine) concentration in the human epidermis. The skin treated with our verum formulation showed a statistically significant 20% decrease in DNA damage compared to placebo. In conclusion, it was demonstrated that SLN technology enabled peptide delivery into skin allowing it to perform protective functions.

Observation of Corneal Langerhans Cells by In Vivo Confocal Microscopy in Thyroid-Associated Ophthalmopathy

ABSTRACT Purpose: To examine the density and morphology of Langerhans cells (LCs) in the cornea of patients with thyroid-associated ophthalmopathy (TAO). Methods: Forty patients with TAO and 20 healthy volunteers were studied. All subjects underwent a thorough ophthalmic examination of both eyes. The ocular surface status was assessed by Ocular Surface Disease Index (OSDI) symptom questionnaires, tear break-up time (BUT), fluorescein staining and the Schirmer test. Laser scanning in vivo confocal microscopy was applied to evaluate the LC density and morphology in both central and peripheral cornea. The correlations between confocal microscopy data and clinical data were also analyzed. Results: The OSDI and fluorescein staining values were significantly higher, while BUT and Schirmer test scores were lower in both active and inactive TAO patients compared to the controls. Central LC densities of patients with active TAO (76.38 ± 67.77 cell/mm2) and inactive TAO (47.49 ± 38.58 cell/mm2) were both significantly higher than those of the controls (21.46 ± 21.74 cell/mm2). The number of LCs in the peripheral cornea was also significantly increased in the active TAO group (131.53 ± 74.18 cell/mm2) compared to the control group (70.21 ± 37.76 cell/mm2). Central LC morphology (LCM) values were significantly higher in both active (1.77 ± 0.63) and inactive (1.51 ± 0.63) TAO groups compared to the control group (1.01 ± 0.80), whereas peripheral LCM scores of the two TAO groups were increased without statistical significance. There were significant correlations between both central LC density and central LCM scores and clinical data, including clinical activity score, OSDI and Schirmer test scores, and between peripheral LC density and OSDI and Schirmer test scores. No significant correlations were found between peripheral LCM scores and clinical data. Conclusions: The increase of corneal LCs in density and maturation in patients with TAO reflects an activated state of the local immune system, which indicates an inflammatory process in the cornea of TAO.

The HPV16 E7 Oncoprotein Disrupts Dendritic Cell Function and Induces the Systemic Expansion of CD11b(+)Gr1(+) Cells in a Transgenic Mouse Model.

Objective. The aim of this study was to analyze the effects of the HPV16 E7 oncoprotein on dendritic cells (DCs) and CD11b+Gr1+ cells using the K14E7 transgenic mouse model. Materials and Methods. The morphology of DCs was analyzed in male mouse skin on epidermal sheets using immunofluorescence and confocal microscopy. Flow cytometry was used to determine the percentages of DCs and CD11b+Gr1+ cells in different tissues and to evaluate the migration of DCs. Results. In the K14E7 mouse model, the morphology of Langerhans cells and the migratory activity of dendritic cells were abnormal. An increase in CD11b+Gr1+ cells was observed in the blood and skin of K14E7 mice, and molecules related to CD11b+Gr1+ chemoattraction (MCP1 and S100A9) were upregulated. Conclusions. These data suggest that the HPV16 E7 oncoprotein impairs the function and morphology of DCs and induces the systemic accumulation of CD11b+Gr1+ cells.

Dry eye and corneal langerhans cells in systemic lupus erythematosus.

Purpose. Investigation of dry eye and corneal Langerhans cells (LCs) in systemic lupus erythematosus (SLE). Methods. Prospective consecutive case series of 27 SLE patients and 27 control subjects. Dry eye was evaluated by lid-parallel conjunctival folds (LIPCOF), Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) questionnaire. In vivo investigation of corneal LCs density and morphology (LCM) was performed with confocal corneal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Module). Results. Tear production and stability were pathological in SLE subjects compared to control (Schirmer: 8.45 ± 9.82 mm/5 min versus 11.67 ± 3.21 mm/5 min; TBUT: 6.86 ± 3.53 s versus 11.09 ± 3.37 s). OSDI was significantly greater in SLE patients (25.95 ± 17.92) than in controls (11.06 ± 7.18). Central LC density was greater in SLE patients (43.08 ± 48.67 cell/mm2) than in controls (20.57 ± 21.04 cell/mm2). There was no difference in the peripheral LC density (124.78 ± 165.39 versus 78.00 ± 39.51 cell/mm2). LCM was higher in SLE patients in the centre (1.43 ± 0.79) and in the periphery (2.89 ± 0.42) compared to controls (centre: 1.00 ± 0.69, periphery: 2.35 ± 0.54). Conclusions. Significant changes in dry eye parameters and marked increase of central LCs could be demonstrated in SLE patients. SLE alters not only the LC density but also the morphology, modifies corneal homeostasis, and might contribute to the development of dry eye.

Effective blue light photodynamic therapy does not affect cutaneous langerhans cell number or oxidatively damage DNA.

Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue light or red light is effective for treating actinic keratoses (AKs). However, immunosuppression follows red light PDT, raising the spectre of skin cancer promotion in treated skin. To determine whether broad-area short incubation (BASI)-ALA-PDT using blue light immunosuppression immunosuppresses treated skin. Patients were evaluated clinically and by standardized facial biopsies of non-AK skin before, 24 hours and 1 month after customary blue light BASI-ALA-PDT. All biopsies were stained for markers of epidermal atypia and Langerhans cells (LCs); and at 24 hours to detect oxidative DNA damage. Patients had an 81% reduction in AKs and slight improvement in clinical and histologic signs of photoaging after 1 month. The biopsied chronically photodamaged skin without clinically detectable AKs showed no effect of PDT on the LC number, distribution, or morphology; and no oxidative DNA damage, in contrast to the changes reported after customary red light PDT. Customary blue light BASI-ALA-PDT does not affect the LC number or produce oxidative DNA damage, the sequelae of red light PDT responsible for immunosuppression in treated skin.

Different subsets of Langerhans cells in human uterine tubes and uterus.

Langerhans cells (LC) are antigen-presenting cells present in tissues with high antigenic exposure. Their role in the upper female reproductive tract is not fully understood. This study aims to determine the distribution and morphology of LC in the normal and post-partum human uterine tubes and uterus by staining with the specific LC markers, CD1a and zinc iodide-osmium (ZIO), and to determine their association with helper and cytotoxic T cells. Normal and post-partum uterine tube and uterine specimens were stained with CD1a and ZIO and their morphology and distribution noted. Double immune staining with CD1a-CD4 and CD1a-CD8 in post-partum uterine tube were also done. It was noted that CD1a-positive cells were significantly fewer and smaller in diameter than ZIO-positive cells in the uterine tube and both types of cells were significantly more prevalent in post-partum tubes. Perivascular clusters of ZIO-positive cells were seen in the post-partum tubes. Close association of CD1a-positive cells with CD4- and CD8-positive T cells was noted in the post-partum uterine tube. In the uterus, scanty CD1a-positive cells were present in the surface and glandular epithelium and endometrial stroma. ZIO-positive cells were absent. This study suggests that CD1a-positive and ZIO-positive cells may be different subsets of LC that are needed for presentation of antigen to immunocompetent cells. Their respective functions are yet to be determined.

Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System.

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

HIV-1 induced autophagy modulation in Langerhans cells

Background and aim Our research aims to decipher the mechanism and immune consequences imposed by HIV-mediated modulation of autophagy in challenged dendritic cell (DC) subsets, in particular Langerhans cells (LC). Autophagy is an ubiquitous cellular process involved in lysosomalmediated degradation of host components as well as invading pathogens. In previous reports, HIV-1 was shown to modulate the autophagy flux in various immune cell types, including T cells, macrophages and myeloid dendritic cells. However, very little is known about the potential autophagy-driven antiviral activity in LC. Methods LC used for this study were differentiated from either blood monocytes or the MUTZ-3 cell line model which phenotypically mimic LC morphology and immune features. LC were treated with wild type HIV-1, VSV-G pseudotyped HIV-1-derived lentivectors or recombinant HIV-1 envelopes. Levels of infection and cellular autophagy flux were analyzed by western blotting, FACS and confocal imaging. Results We observe that, as previously described for myeloid DC, autophagy flux is compromised in LC after exposure to HIV-1 envelope or infectious virus. Hence, activation of the autophagy negative regulator, mTOR, is detected, and could account for the autophagy flux inhibition. Although we could confirm the HIV-1 restriction activity of langerin and SAMHD-1 in LC, it appears that shutting down autophagy flux is an early cellular target for the virus thus strongly suggesting that it might be involved in HIV-1 clearance shortly upon viral entry. Conclusion In this study, we show that Langerin and SAMHD-1 are significantly restricting HIV-1 entry and replication in LC. However, an additional barrier to infection, such as autophagolysosome-mediated degradation of virus particles, may account for the low infection rate observed in LC. Our results suggest that autophagy flux is indeed dampened upon HIV-1 challenge which might favour virus progression. We further aim to examine the effect of autophagy modulation on virus infection of LC and consequent virus transmission to CD4 + T cells.

Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis

APCs of the ocular surface, including corneal Langerhans cells (LCs), offer the opportunity to gain insight into the activity of innate immunity. We examined corneal LCs and dry eye parameters in ankylosing spondylitis (AS). Twenty-four AS patients with varying degrees of disease activity and 24 healthy participants were enrolled. Central and peripheral LC numbers, and Langerhans cell morphology (LCM) were assessed with invivo laser confocal microscopy. In addition, ocular surface disease index, lid parallel conjunctival folds, tear break up time, and Schirmer test were evaluated. LC densities and central LCM were greater in AS patients than in the controls. Moreover, LCM was significantly greater in patients with higher systemic inflammation according to elevated C-reactive protein (CRP). Also, tear production was greatly suppressed in patients with more severe onset of the systemic inflammation according to the Bath Ankylosing Spondylitis Disease Activity Index and elevated CRP. Greater corneal LC density and LCM in AS may reflect an increased activation state of the innate immune system of the cornea in AS, which correlates with the systemic activity of AS even without ocular symptoms. Nonetheless, higher systemic inflammation might impair tear production, and it might partly explain the dry eye mechanism.

Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis

AbstractPurpose To examine the density and the distribution of corneal Langerhans cells (LCs) and to compare the results with dry‐eye related parameters and disease activity in ankylosing spondylitis(AS).Methods Twenty four AS patients (mean age: 41.8±9.8 years) with various degree of disease activity and twenty four healthy subjects (mean age: 47.9 ± 16.4 years) were enrolled. Ocular surface disease index (OSDI), lid parallel conjunctival folds (LIPCOF), tear break up time (TBUT), and Schirmer test (ST) were evaluated. In addition, central and peripheral LCs numbers and Langerhans cell morphology (LCM) were assessed with in vivo laser confocal microscopy.Results Tear production was greatly suppressed in patients with more severe systemic inflammation according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C‐reactive protein (CRP) (BASDAI≤4.0 vs BASDAI&gt;4.0 10.2±8.5 vs 4.0±5.3; CRP≤5.0 vs CRP&gt;5.0 17.2±4.2 vs 3.9±5.5 p&lt;0.05 for all). LCs densities and central LCM were greater in AS patients than in the controls (LC density: 77.5±44.9 vs 23.8±33.8 and central LCM: 1.7±0.7 vs 0.95±0.75 p&lt;0.05 for all).Conclusion Greater corneal LC density and LCM may reflect an increased activation of the corneal innate immune system, which correlates with the systemic activity of AS even without ocular symptoms. Higher systemic inflammation might impair tear production, and it might partly explain the dry eye mechanism.