Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease

• DOI: 10.1038/s41467-017-02683-x
• Publication Date: 2018-01-10T23:13:36Z
• Authors: Xianyi Meng; Bettina Grötsch; Yubin Luo; Karl Xaver Knaup; Michael Sean Wies...; Xiao-Xiang Chen; Jonathan Jantsch; Simon Fillatreau; Georg Schett; Aline Bozec
• Keywords: 0301 basic medicine; B-Lymphocytes; Science; Q; Hypoxia-Inducible Factor 1, alpha Subunit; Arthritis, Experimental; Article; Autoimmune Diseases; Interleukin-10; 3. Good health; Mice; 03 medical and health sciences; Animals; Encephalomyelitis

AbstractHypoxia-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 CD1dhiCD5+ 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 CD1dhiCD5+ B cells, but not Hif1a-deficient CD1dhiCD5+ B cells, protect recipient mice from autoimmune disease, while the protective function of Hif1a-deficient CD1dhiCD5+ 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 CD1dhiCD5+ B cells, and in controlling their protective activity in autoimmune disease.