<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The role of EBI2 in inflammatory skin diseases"^^ . "Epstein-Barr virus-induced gene 2 (EBI2), also known as G protein-coupled receptor 183 (GPR183), is a chemotactic receptor. Its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) is an oxysterol and is produced by the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily B member 1 (CYP7B1). The EBI2-oxysterol axis has been shown to be critical for the correct development and microanatomical positioning of immune cells in primary and secondary lymphoid organs (SLOs). It is part of the chemotactic network that guides the intricate intranodal migration of B cells, T cells, and dendritic cells. Deficiency in EBI2 or CH25H leads to impaired B- and T cell priming. In line with its chemotactic function in SLOs, the EBI2-oxysterol axis has been associated with several disease pathologies. There, it was shown to be involved in the recruitment of pathogenic cells and formation of tertiary lymphoid structures in diseases affecting the joints, the lung, the central nervous system, and the intestine. Recent reports also suggest a contribution of the EBI2-oxysterol axis in the pathogenesis of inflammatory skin diseases; however, conclusive studies are missing. Tissue-resident memory T (TRM) cells are known drivers of peripheral diseases. They are especially well described in the skin, where they mediate site-specific relapses of chronic inflammatory disorders. To date, nothing is known about the connection between the EBI2-oxysterol axis, inflammatory skin diseases and TRM cells.\r\nHere I show that EBI2 expression is a characteristic feature of TRM cells. Utilizing an EBI2-enhanced green fluorescent protein (EGFP) knock-in mouse line that functions both as a reporter and a knock-out, I found that murine TRM cell progenitor cells upregulate EBI2 during differentiation to TRM cells in the skin. Consequently, murine skin TRM cells highly express EBI2. In contrast, only minor proportions of circulating CD8+ naïve and memory T cells express EBI2. This induction of EBI2 on TRM cells suggests a functional relevance. Similarly, I found that the majority of TRM cells from healthy human skin also expresses EBI2. I therefore launched a clinical study to analyze skin biopsies from psoriasis patients using high parameter flow cytometry. While TRM cells from non-lesional and lesional skin showed similar EBI2 expression, I found that the EBI2 expression level was associated with a functional dichotomy. EBI2high TRM cells showed higher proportions of effector molecule-producing cells than EBI2low TRM cells. They were further enriched in cells producing granzyme B, interferon-γ, interleukin-10, and Ki-67 and decreased in cells expressing the exhaustion marker CD101. This suggests that EBI2 is part of the TRM1 phenotype, shown to be an important mediator of vitiligo and host defense. It will therefore be interesting to investigate the role of the EBI2-oxysterol axis in vitiligo pathogenesis and viral infection. However, in mice, EBI2 deficiency had no impact on TRM cell generation, retention, subset distribution, or on allergic contact dermatitis and psoriasis mouse models. Collaboration partners showed that EBI2 is also expressed by human lung and colon TRM cells. Elucidating the role of EBI2 on TRM cells and its involvement in TRM cell-mediated host defense and skin disease pathogenesis is therefore an interesting topic for future investigations with potential therapeutical implications."^^ . "2025" . . . . . . . "Lucas Til"^^ . "Arendholz"^^ . "Lucas Til Arendholz"^^ . . . . . . "The role of EBI2 in inflammatory skin diseases (PDF)"^^ . . . "The role of EBI2 in inflammatory skin diseases (Other)"^^ . . . . . . "The role of EBI2 in inflammatory skin diseases (Other)"^^ . . . . . . "The role of EBI2 in inflammatory skin diseases (Other)"^^ . . . . . . "The role of EBI2 in inflammatory skin diseases (Other)"^^ . . . . . . "The role of EBI2 in inflammatory skin diseases (Other)"^^ . . . . . "HTML Summary of #34780 \n\nThe role of EBI2 in inflammatory skin diseases\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .