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

Xianyi Meng, Bettina Grötsch, Yubin Luo, Karl Xaver Knaup, Michael Sean Wiesener, Xiao-Xiang Chen, Jonathan Jantsch, Simon Fillatreau, Georg Schett and Aline Bozec ()
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Xianyi Meng: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Bettina Grötsch: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Yubin Luo: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Karl Xaver Knaup: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Michael Sean Wiesener: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Xiao-Xiang Chen: Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jonathan Jantsch: University of Regensburg
Simon Fillatreau: Université Paris Descartes
Georg Schett: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Aline Bozec: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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-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.

Date: 2018
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DOI: 10.1038/s41467-017-02683-x

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