Glutaminolysis is required in maintaining immune regulatory functions in B cells

• Published in: Mucosal immunology Vol. 15; no. 2; pp. 268 - 278
• Main Authors: Liu, Jiang-Qi, Geng, Xiao-Rui, Hu, Tian-Yong, Mo, Li-Hua, Luo, Xiang-Qian, Qiu, Shu-Yao, Liu, Da-Bo, Liu, Zhi-Gang, Shao, Jian-Bo, Liu, Zhi-Qiang, Yang, Ping-Chang
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2022; Elsevier Limited
• Subjects: Allergic rhinitis; Allergology; Amino acids; Antibodies; B-Lymphocytes, Regulatory - metabolism; Biomedical and Life Sciences; Biomedicine; CD4-Positive T-Lymphocytes; Cell activation; Flow Cytometry; Gastroenterology; Glutamine; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 - metabolism; Humans; Immunology; Immunoregulation; Interleukin 10; Lymphocyte Count; Lymphocytes B; Lymphocytes T; Peripheral blood; Rhinitis; TOR protein
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-021-00481-9

IL-10-expressing regulatory B cells (B10 cells) are dysfunctional in patients with many immune disorders. The underlying mechanism remains to be further elucidated. Glutamine is an essential nutrient for cell metabolism. This study aims to elucidate the role of glutaminolysis in maintaining the immune regulatory capacity in B10 cells. Peripheral blood samples were collected from 50 patients with allergic rhinitis and 50 healthy control subjects. B cells were isolated from blood samples by cell sorting with flow cytometry. The role of glutaminolysis in regulating B10 cell activities was assessed by immunological and biochemical approaches. The results showed that B cells from patients with allergic rhinitis expressed low levels of the transporter of glutamine and neutral amino acid. Glutaminolysis was required in the IL-10 expression in B cells. The glutamine catabolism was required in B10 cell generation. The mTOR activation mediated the glutaminolysis-associated B10 cell induction, and the suppression of the B cell glycogen synthase kinase-3 (GSK3) activation. GSK3 activation suppressed IL-10 expression in B cells. Inhibition of GSK3 enhanced IL-10 expression in B cells and alleviated experimental allergic rhinitis by generating immune competent type 1 regulatory T cells.