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The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus.


ABSTRACT: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN-I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25-dihydroxycholesterol (7α, 25-OHC), are identified in SLE patients. The authors find that 7α, 25-OHC binding to its receptor Epstein-Barr virus-induced gene 2 (EBI2) in macrophages can suppress STAT activation and the production of IFN-β, chemokines, and cytokines. Importantly, monocytes/macrophages from SLE patients and mice show significantly reduced EBI2 expression, which can be triggered by IFN-γ produced in activated T cells. Previous findings suggest that EBI2 enhances immune cell migration. Opposite to this effect, the authors demonstrate that EBI2-deficient macrophages produce higher levels of chemokines and cytokines, which recruits and activates myeloid cells,T and B lymphocytes to exacerbate tetramethylpentadecane-induced SLE. Together, via sensing the oxysterol 7α, 25-OHC, EBI2 in macrophages can modulate innate and adaptive immune responses, which may be used as a potential diagnostic marker and therapeutic target for SLE.

SUBMITTER: Zhang F 

PROVIDER: S-EPMC10520634 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus.

Zhang Fang F   Zhang Baokai B   Ding Huihua H   Li Xiangyue X   Wang Xilin X   Zhang Xiaomin X   Liu Qiaojie Q   Feng Qiuyun Q   Han Mingshun M   Chen Longlong L   Qi Linlin L   Yang Dan D   Li Xiaojing X   Zhu Xingguo X   Zhao Qi Q   Qiu Jiaqian J   Zhu Zhengjiang Z   Tang Huiru H   Shen Nan N   Wang Hongyan H   Wei Bin B  

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230719 27


Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN-I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25-dihydroxycholesterol (7α, 25-OHC), are identified in SLE patients. The authors find th  ...[more]

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