1. Academic Validation
  2. Glutaminolysis is required in maintaining immune regulatory functions in B cells

Glutaminolysis is required in maintaining immune regulatory functions in B cells

  • Mucosal Immunol. 2022 Feb;15(2):268-278. doi: 10.1038/s41385-021-00481-9.
Jiang-Qi Liu  # 1 Xiao-Rui Geng  # 1 Tian-Yong Hu  # 1 Li-Hua Mo 2 3 Xiang-Qian Luo 4 Shu-Yao Qiu 4 Da-Bo Liu 4 Zhi-Gang Liu 2 3 Jian-Bo Shao 5 Zhi-Qiang Liu 6 Ping-Chang Yang 7 8 9
Affiliations

Affiliations

  • 1 Department of Otolaryngology, Longgang E.N.T hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T Shenzhen, Shenzhen, China.
  • 2 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.
  • 3 Institute of Allergy & Immunology, Shenzhen University School of Medicine, State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China.
  • 4 Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
  • 5 Department of Otolaryngology, Beijing Children Hospital, Beijing, China.
  • 6 Department of Otolaryngology, Longgang E.N.T hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T Shenzhen, Shenzhen, China. liuzhiqiang05312438@126.com.
  • 7 Department of Otolaryngology, Longgang E.N.T hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T Shenzhen, Shenzhen, China. pcy2356@163.com.
  • 8 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China. pcy2356@163.com.
  • 9 Institute of Allergy & Immunology, Shenzhen University School of Medicine, State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China. pcy2356@163.com.
  • # Contributed equally.
Abstract

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.

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