Glutaminolysis is required in maintaining immune regulatory functions in B cells

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.

Automated summary

This study reveals that glutaminolysis plays a critical role in maintaining the immune regulatory capacity of IL-10-expressing B cells (B10 cells) in patients with allergic rhinitis. Glutamine metabolism is necessary for IL-10 expression in B cells and the generation of B10 cells. The activation of mTOR mediates the induction of glutaminolysis-associated B10 cells and suppresses the activation of B cell glycogen synthase kinase-3 (GSK3). GSK3 activation inhibits IL-10 expression in B cells.