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Oxysterols regulate CD4+ T cell trafficking during experimental autoimmune encephalomyelitis

Chalmin, Fanny and Rochemont, Viviane and Lippens, Carla and Clottu, A and Sailer, Andreas and Merkler, Doron and Hugues, Stephanie and Pot, Caroline (2015) Oxysterols regulate CD4+ T cell trafficking during experimental autoimmune encephalomyelitis. Journal of Autoimmunity, 56. pp. 45-55.

Abstract

Perturbation of steroids pathways has been linked to inflammation and chronic diseases. Oxysterols, oxidised forms of cholesterol, are essential for bile synthesis biosynthesis and sterol transportation. In addition to their basic metabolic properties, oxysterols modulate immune response and control trafficking of immune cells such as B lymphocytes and macrophages. Furthermore, serum oxysterols levels have been proposed as putative candidate biomarkers for neurological diseases such as Multiple sclerosis (MS). The enzyme cholesterol 25 hydroxylase (ch25h) is the rate limiting step to synthetize the oxysterol 7,25-dihydroxycholesterol (725-OHC) from cholesterol. We here report, using the MS murine model experimental autoimmune encephalomyelitis (EAE), that deletion of ch25h attenuated EAE disease course by dampening pathogenic T lymphocytes trafficking to the central nervous system (CNS). While systemic immune response is preserved in the absence of ch25h, IL-17 producing CD4+ T helper (TH17) cells accumulate in the draining lymph nodes. Furthermore, TH17 cells migrate towards 725-OHC in an Epstein-Barr virus-induced G-protein coupled receptor 2 (ebi2) dependent-manner. Collectively, our results reveal a critical involvement for oxysterols in migration of distinct subset of CD4+ T lymphocytes thus supporting a pro-inflammatory role for oxysterols during EAE.

Item Type: Article
Keywords: CH25H; oxysterol
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21361

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