Obeticholic acid alleviates lupus pathology by inhibiting T follicular helper cell differentiation.

Authors

Minjung Kang, Jiho Park, Jongeun Lee, Sung Won Kim, Yoontae Lee

Published in

EMBO molecular medicine. Jul 03, 2026. Epub Jul 03, 2026.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant germinal center (GC) reactions and autoantibody production. Expansion of T follicular helper (T_FH) cells is a hallmark of SLE that contributes to disease progression. Accordingly, T_FH cells represent a promising therapeutic target for SLE. Here, we repurposed obeticholic acid (OCA), an FDA-approved drug for primary biliary cholangitis, as a potential treatment for SLE. OCA selectively inhibited the differentiation of T_FH cells both in vitro and in vivo by suppressing the transcription factor ETV5, thereby downregulating SPP1, a key ETV5 target that promotes the development of T_FH cells. In lupus-prone mice, OCA treatment reduced T_FH- and GC B-cell populations and alleviated lupus-like manifestations, including autoantibody production and tissue pathology. These findings highlight OCA as a promising immunomodulatory candidate for SLE, providing avenues for devising a therapeutic strategy targeting the T_FH cell-GC axis in systemic autoimmunity.

PMID:
42399404
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.

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