Zusammenfassung
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-1 alpha (HIF-1 alpha) contributes to IL-10 production by B cells. HIF-1 alpha regulates IL-10 expression, and HIF-1 ...
Zusammenfassung
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-1 alpha (HIF-1 alpha) contributes to IL-10 production by B cells. HIF-1 alpha regulates IL-10 expression, and HIF-1 alpha-dependent glycolysis facilitates CD1d(hi)CD5(+) 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(hi)CD5(+) B cells, but not Hif1a-deficient CD1d(hi)CD(5+) B cells, protect recipient mice from autoimmune disease, while the protective function of Hif1a-deficient CD1d(hi)CD(5+) 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-1 alpha in driving IL-10 expression in CD1d(hi)CD5(+) B cells, and in controlling their protective activity in autoimmune disease.
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