GABA signaling enforces intestinal germinal center B cell differentiation.

ABSTRACT: Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA⁺ B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA-mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling-mediated intestinal mucosal immunity as

SUBMITTER: Liao Y 

PROVIDER: S-EPMC9636909 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature