| First Author | Meng X | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 251 |
| PubMed ID | 29343683 | Mgi Jnum | J:259999 |
| Mgi Id | MGI:6114833 | Doi | 10.1038/s41467-017-02683-x |
| Citation | Meng X, et al. (2018) Hypoxia-inducible factor-1alpha is a critical transcription factor for IL-10-producing B cells in autoimmune disease. Nat Commun 9(1):251 |
| abstractText | 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-1alpha (HIF-1alpha) contributes to IL-10 production by B cells. HIF-1alpha regulates IL-10 expression, and HIF-1alpha-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)CD5(+) B cells, protect recipient mice from autoimmune disease, while the protective function of Hif1a-deficient CD1d(hi)CD5(+) 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-1alpha in driving IL-10 expression in CD1d(hi)CD5(+) B cells, and in controlling their protective activity in autoimmune disease. |
