Thrombomodulin (TM) is a protein, present on intact endothelial cell surfaces, that plays a major role in the protein C anticoagulant system. Plasma TM is produced by injured endothelium, and is recognized in circulating blood or urine as a sign of endothelium cell damage. The localization of TM within the eye and its kinetics in the eye and the serum were investigated in rats with experimental autoimmune uveoretinitis (EAU). An immuno-histochemical study showed the presence of TM at sites of fibrin in the anterior chamber and retinal vasculitis. The amount of TM in the eye increased with progression of intraocular inflammation, but the serum level of TM did not significantly differ from the values in the control group. These data suggest that TM may play a role in preventing thrombosis in cases of vasculitis and fibrin formation in the anterior chamber in EAU, thus maintaining blood flow and the fluidity of aqueous humor.
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Nat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
View Article and Find Full Text PDFBrain Behav Immun
January 2025
Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, Heilongjiang, PR China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin 150081, Heilongjiang, PR China. Electronic address:
It has been reported that the nervous system can regulate immune reactions through various mechanisms. However, the role of splenic sympathetic nerve activity in the autoimmune reactions during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) remained unclear. Here, we blocked the activity of the splenic sympathetic nerve and found that the number of adaptive immune cells, such as CD4 T cells, CD8 T cells and B cells, were upregulated.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China.
Circadian rhythm plays a critical role in the progression of autoimmune diseases. While our previous study demonstrated the therapeutic effects of melatonin in experimental autoimmune uveitis, the involvement of circadian rhythm remained unclear. Using a light-induced circadian rhythm disruption model, we showed that disrupted circadian rhythms exacerbate autoimmune uveitis by impairing the stability and function of Treg cells.
View Article and Find Full Text PDFMuscle Nerve
January 2025
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Introduction/aims: Tofacitinib, a first-generation Janus kinase (JAK) 1/3 inhibitor, is commonly used for treating ulcerative colitis and rheumatoid arthritis. However, its role in myasthenia gravis (MG) remains unclear. This study aimed to evaluate the immunomodulatory effects of tofacitinib on experimental autoimmune myasthenia gravis (EAMG) and peripheral blood mononuclear cells (PBMCs) from patients with MG.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
March 2025
Institute for Clinical Neurobiology, University Hospital, Julius-Maximilians-University of Würzburg, Germany.
Background And Objectives: Autoantibodies (aAbs) against glycine receptors (GlyRs) are mainly associated with the rare neurologic diseases stiff person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM). GlyR aAbs are also found in other neurologic diseases such as epilepsy. The aAbs bind to different GlyR α-subunits and, more rarely, also to the GlyR β-subunit.
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