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

Meng X, Groetsch B, Luo Y, Knaup K, Wiesener MS, Chen XX, Jantsch J, Fillatreau S, Schett G, Bozec A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 9

Pages Range: 251

Journal Issue: 1

DOI: 10.1038/s41467-017-02683-x

Abstract

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? (HIF-1?) contributes to IL-10 production by B cells. HIF-1? regulates IL-10 expression, and HIF-1?-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-1? in driving IL-10 expression in CD1dhiCD5+ B cells, and in controlling their protective activity in autoimmune disease.

Authors with CRIS profile

Xianyi Meng Juniorprofessur für Osteoimmunologie Karl Knaup Department of Medicine 4 – Nephrology and Hypertension Georg Schett Lehrstuhl für Innere Medizin III Aline Bozec Juniorprofessur für Osteoimmunologie

Involved external institutions

University of Paris 5 - René Descartes / Université Paris V René Descartes FR France (FR) Universität Regensburg DE Germany (DE) Shanghai Jiao Tong University / 上海交通大学 CN China (CN)

How to cite

APA:

Meng, X., Groetsch, B., Luo, Y., Knaup, K., Wiesener, M.S., Chen, X.-X.,... Bozec, A. (2018). Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease. Nature Communications, 9(1), 251. https://dx.doi.org/10.1038/s41467-017-02683-x

MLA:

Meng, Xianyi, et al. "Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease." Nature Communications 9.1 (2018): 251.

BibTeX: Download