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Publication : The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation.

First Author  Jegodzinski L Year  2020
Journal  Front Immunol Volume  11
Pages  1858 PubMed ID  32922401
Mgi Jnum  J:308211 Mgi Id  MGI:6714601
Doi  10.3389/fimmu.2020.01858 Citation  Jegodzinski L, et al. (2020) The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation. Front Immunol 11:1858
abstractText  The G protein-coupled receptor 15 (GPR15) has recently been highlighted as an important regulator of T cell trafficking into the gut under physiological and pathophysiological conditions. Additionally, circumstantial evidence has accumulated that GPR15 may also play a role in the regulation of chronic inflammation. However, the (patho)physiological significance of GPR15 has, in general, remained rather enigmatic. In the present study, we have addressed the role of GPR15 in the effector phase of autoantibody-mediated skin inflammation, specifically in the antibody transfer mouse model of bullous pemphigoid-like epidermolysis bullosa acquisita (BP-like EBA). Subjecting Gpr15 (-/-) mice to this model, we have uncovered that GPR15 counteracts skin inflammation. Thus, disease was markedly aggravated in Gpr15 (-/-) mice, which was associated with an increased accumulation of gammadelta T cells in the dermis. Furthermore, GPR15L, the recently discovered cognate ligand of GPR15, was markedly upregulated in inflamed skin. Collectively, our results highlight GPR15 as counter-regulator of neutrophilic, antibody-mediated cutaneous inflammation. Enhancing the activity of GPR15 may therefore constitute a novel therapeutic principle in the treatment of pemphigoid diseases, such as BP-like EBA.
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