Oxysterols regulate encephalitogenic CD4<sup>+</sup> T cell trafficking during central nervous system autoimmunity

Chalmin, Fanny; Rochemont, Viviane; Lippens, Carla; Clottu, Aurélie Sarah; Sailer, A W; Merkler, Doron; Hugues, Stéphanie; Pot, Caroline

doi:10.1016/j.jaut.2014.10.001

Scientific article

English

Oxysterols regulate encephalitogenic CD4⁺ T cell trafficking during central nervous system autoimmunity

Contributors

Chalmin, Fanny; Rochemont, Viviane; Lippens, Carla; Clottu, Aurélie Sarah; Sailer, A W; Merkler, Doron

; Hugues, Stéphanie; Pot, Caroline

Published in

Journal of autoimmunity, vol. 56, p. 45-55

Publication date

2015

Abstract

Perturbation of steroids pathways is linked to inflammation and chronic diseases, however the underlying mechanism remains unclear. Oxysterols, oxidized forms of cholesterol, are not only essential for bile synthesis and sterol transportation but have recently been shown to contribute to the immune response. In addition, serum oxysterols levels have been proposed as suitable candidate biomarkers for neurological diseases such as multiple sclerosis (MS). However how oxysterols modulate adaptive immunity is unknown and their functions in autoimmunity have not been investigated. The enzyme cholesterol 25 hydroxylase (Ch25h) is the rate limiting step to synthesize the oxysterol 7α,25-dihydroxycholesterol (7α,25-OHC) from cholesterol. We here report, using the MS murine model experimental autoimmune encephalomyelitis (EAE), that Ch25h deletion significantly attenuated EAE disease course by limiting trafficking of pathogenic CD4(+) T lymphocytes to the central nervous system (CNS). Mechanistically, we show a critical involvement for oxysterols in recruiting leukocytes into inflamed tissues and propose that 7α,25-OHC preferentially promotes the migration of activated CD44(+)CD4(+) T cells by binding the G protein-coupled receptor called Epstein-Barr virus induced gene 2 (EBI2). Collectively, our results support a pro-inflammatory role for oxysterols during EAE and identify oxysterols as a potential therapeutic target to treat autoimmune diseases.

UNIGE affiliation entities

UNIGE research groups

Funding

Swiss National Science Foundation - Viral triggers and gray matter involvement in multiple sclerosis [128372]

Citation (ISO format)

CHALMIN, Fanny et al. Oxysterols regulate encephalitogenic CD4⁺ T cell trafficking during central nervous system autoimmunity. In: Journal of autoimmunity, 2015, vol. 56, p. 45–55. doi: 10.1016/j.jaut.2014.10.001

Article (Published version)

Identifiers

PID : unige:45174
DOI : 10.1016/j.jaut.2014.10.001
PMID : 25456971

Journal ISSN

0896-8411

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Creation

03/12/2014 13:25:00

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03/12/2014 13:25:00

Update

13/10/2025 21:55:28

Status update

20/01/2025 09:36:02

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02/11/2026 16:26:27

Oxysterols regulate encephalitogenic CD4⁺ T cell trafficking during central nervous system autoimmunity

Contributors

Published in

Publication date

Abstract

UNIGE affiliation entities

UNIGE research groups

Funding

Citation (ISO format)

Main files (1)

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Journal ISSN

Technical informations

Creation

First validation

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Status update

Last indexation

Oxysterols regulate encephalitogenic CD4+ T cell trafficking during central nervous system autoimmunity

Contributors

Published in

Publication date

Abstract

UNIGE affiliation entities

UNIGE research groups

Funding

Citation (ISO format)

Main files (1)

Identifiers

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation

Oxysterols regulate encephalitogenic CD4⁺ T cell trafficking during central nervous system autoimmunity