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Differential Expression of ARG1 and MRC2 in Retinal Müller Glial Cells During Autoimmune Uveitis

Affiliation
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany(T.W.)
Fleischer, Amelie B.;
Affiliation
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany(T.W.)
Amann, Barbara;
Affiliation
Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health, D-80939 Munich, Germany
von Toerne, Christine;
ORCID
0000-0003-2680-7227
Affiliation
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany(T.W.)
Degroote, Roxane L.;
ORCID
0000-0003-2462-2675
Affiliation
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany(T.W.)
Schmalen, Adrian;
Affiliation
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany(T.W.)
Weißer, Tanja;
Affiliation
Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health, D-80939 Munich, Germany
Hauck, Stefanie M.;
ORCID
0000-0003-0375-3190
Affiliation
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany(T.W.)
Deeg, Cornelia A.

Retinal Müller glial cells (RMG) play a crucial role in retinal neuroinflammation, including autoimmune uveitis. Increasing evidence supports their function as active modulators of immune responses and potential atypical antigen-presenting cells (APCs). To further investigate this hypothesis, we conducted a differential proteome analysis of primary equine RMG from healthy controls and horses with equine recurrent uveitis (ERU), a spontaneous model of autoimmune uveitis. This analysis identified 310 proteins with differential abundance. Among these, the Major Histocompatibility Complex (MHC) class II and the enzyme Arginase 1 (ARG1) were significantly enriched in RMG from uveitis-affected horses, whereas Mannose Receptor C-type 2 (MRC2) and its interactor Thrombospondin 1 (THBS1) were more abundant in healthy RMG. The detection of MHC class II in equine RMG, consistent with previous studies, validates the robustness of our approach. Furthermore, the identification of ARG1 and MRC2, together with THBS1, provides new insights into the immunomodulatory and antigen-presenting properties of RMG. Immunohistochemical analyses confirmed the proteomic findings and revealed the spatial distribution of ARG1 and MRC2. ARG1 and MRC2 are thus markers for RMG in the neuroinflammatory or physiological milieu and highlight potential differences in the immune function of RMG, particularly in antigen presentation.

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