Hypoxia-inducible factors (HIFs) are key elements for controlling immune cell metabolism and functions. While HIFs are known to be involved in T cells and macrophages activation, their functions in B lymphocytes are poorly defined. Here, we show that hypoxia-inducible factor-1α (HIF-1α) contributes to IL-10 production by B cells. HIF-1α regulates IL-10 expression, and HIF-1α-dependent glycolysis facilitates CD1d^hiCD5⁺ B cells expansion. Mice with B cell-specific deletion of Hif1a have reduced number of IL-10-producing B cells, which result in exacerbated collagen-induced arthritis and experimental autoimmune encephalomyelitis. Wild-type CD1d^hiCD5⁺ B cells, but not Hif1a-deficient CD1d^hiCD5⁺ B cells, protect recipient mice from autoimmune disease, while the protective function of Hif1a-deficient CD1d^hiCD5⁺ B cells is restored when their defective IL-10 expression is genetically corrected. Taken together, this study demonstrates the key function of the hypoxia-associated transcription factor HIF-1α in driving IL-10 expression in CD1d^hiCD5⁺ B cells, and in controlling their protective activity in autoimmune disease.

中文翻译：

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缺氧诱导因子-1α是自身免疫疾病中产生IL-10的B细胞的关键转录因子。

缺氧诱导因子（HIFs）是控制免疫细胞代谢和功能的关键元素。尽管已知HIF参与T细胞和巨噬细胞的活化，但它们在B淋巴细胞中的功能却定义不清。在这里，我们显示缺氧诱导因子-1α（HIF-1α）有助于B细胞产生IL-10。HIF-1α调节IL-10表达，而HIF-1α依赖性糖酵解促进CD1d ^hi CD5 ⁺ B细胞扩增。具有B细胞特异性缺失Hif1a的小鼠减少了产生IL-10的B细胞数量，从而加剧了胶原诱导的关节炎和实验性自身免疫性脑脊髓炎。野生型CD1d ^hi CD5 ⁺ B细胞，但没有Hif1a缺陷型CD1d ^hi CD5 ⁺B细胞可保护受体小鼠免于自身免疫性疾病，而通过基因纠正其缺陷性IL-10表达后，Hif1a缺陷型CD1d ^hi CD5 ⁺ B细胞的保护功能将恢复。综上所述，该研究证明了低氧相关转录因子HIF-1α在驱动CD1d ^hi CD5 ⁺ B细胞中IL-10表达以及控制其在自身免疫性疾病中的保护活性方面的关键功能。