Meng, Xianyi and Groetsch, Bettina and Luo, Yubin and Knaup, Karl Xaver and Wiesener, Michael Sean and Chen, Xiao-Xiang and Jantsch, Jonathan and Fillatreau, Simon and Schett, Georg and Bozec, Aline (2018) Hypoxia-inducible factor-1 alpha is a critical transcription factor for IL-10-producing B cells in autoimmune disease. NATURE COMMUNICATIONS, 9: 251. ISSN 2041-1723,
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROLYL HYDROXYLASE INHIBITION; B10 CELLS; IL-10 PRODUCTION; REGULATORY FUNCTION; HIF-ALPHA; T-CELLS; HIF-1-ALPHA; ACTIVATION; IMMUNITY; DIFFERENTIATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Mar 2020 12:31 |
| Last Modified: | 19 Mar 2020 12:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15192 |
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