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<p>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<sub>FH</sub>) cells is a hallmark of SLE that contributes to disease progression. Accordingly, T<sub>FH</sub> 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<sub>FH</sub> cells both in vitro and in vivo by suppressing the transcription factor ETV5, thereby downregulating <i>SPP1</i>, a key ETV5 target that promotes the development of T<sub>FH</sub> cells. In lupus-prone mice, OCA treatment reduced T<sub>FH</sub>- 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<sub>FH</sub> cell–GC axis in systemic autoimmunity.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月3日

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

摘要

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant germinal center (GC) reactions and autoantibody production. Expansion of T follicular helper (TFH) cells is a hallmark of SLE that contributes to disease progression. Accordingly, TFH 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 TFH 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 TFH cells. In lupus-prone mice, OCA treatment reduced TFH- 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 TFH cell–GC axis in systemic autoimmunity.