AUTHOR=Zhang Qian , Wang Lei , Jiang Jintao , Lin Shiyu , Luo Aishu , Zhao Pengfei , Tan Wenfeng , Zhang Miaojia 

TITLE=Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.02040

DOI=10.3389/fimmu.2020.02040

ISSN=1664-3224

ABSTRACT=<p>We previously reported that adiponectin (AD) promotes naïve T cell differentiation into Th17 cells and participates in synovial inflammation and the bone erosion process in patients with rheumatoid arthritis. Here, we use a T cell lineage adiponectin receptor 1 (AdipoR1) conditional knockout model to investigate the role of AdipoR1 in Th17 differentiation. RNA-sequencing (RNA-seq) demonstrated that <italic>AdipoR1</italic> knockout reduced the expression of a variety of T cell related genes, with <italic>Rorc</italic> showing the greatest level of down-regulation. AdipoR1 deficiency inhibited Th17 cell differentiation <italic>in vitro</italic> and ameliorated joint inflammation in antigen-induced arthritis mice. Moreover, AdipoR1-deficent CD4<sup>+</sup>T cells displayed reduced Hypoxia-Inducible Factor-1α expression leading to glycolysis inhibition during naïve CD4<sup>+</sup>T cell differentiation into Th17 cells. We describe a novel function of AdipoR1 in regulating Th17 cell differentiation through modulating HIF-1α-dependent glycolysis.</p>