Myeloid‐Derived Suppressor Cell–Derived Interferon‐β Promotes T Follicular Helper Cell Response and Exacerbates Lupus Development

作者：Ke Rui, Zixiang Chen, Jun Liu, Wei Huang, Xiaomeng Wang, Fan Xiao, Yingbo Zhou, Xiaoqiu Dai, Yuan Yan Tang, Mengna Zhao, Na Peng, Xiaoran Wang, Bo Zhu, Shengjun Wang, Liwei Lu, Jie Tian · 发表于：Arthritis & Rheumatology · 年份：2025 · DOI：10.1002/art.70004 · 被引用次数：2 · 研究领域：Systemic Lupus Erythematosus Research、interferon and immune responses、Cytokine Signaling Pathways and Interactions

Objective Increasing evidence highlights a critical role of T follicular helper (Tfh) cells in autoimmune pathogenesis. This study aimed to identify inflammatory cytokines involved in driving Tfh cell responses in systemic lupus erythematosus (SLE). Methods The circulating Tfh frequencies and interferon (IFN)‐β levels were analyzed for correlations with disease activities in patients with SLE. Both lupus mice with IFN‐β treatment and Ifnar1 −/− mice with lupus induction were assessed for Tfh cell responses and disease progression. Sorting‐purified naive CD4 + T cells from Ifnar1 −/− mice were adoptively transferred to lupus mice for monitoring Tfh cell differentiation in vivo. In culture, mouse CD4 + T cells treated with IFN‐β were examined for Tfh cell differentiation and intracellular signaling pathway. The underlying mechanism for IFN‐β secretion by myeloid‐derived suppressor cells (MDSCs) was investigated by co‐immunoprecipitation and Western blotting. Results We found that increased Tfh cells with IFN‐I–inducible gene signatures correlated with disease activities in patients with SLE. Consistently, IFN‐β treatment markedly enhanced Tfh cell response and exacerbated disease progression in lupus mice. Moreover, mice with IFNAR1 deficiency exhibited attenuated lupus progression with significantly decreased Tfh response. Mechanistically, IFN‐β activated the indoleamine 2,3‐dioxygenase/kynurenine/aryl hydrocarbon receptor (IDO/Kyn/AhR) axis to promote Tfh cell differentiation...