GABA signaling enforces intestinal germinal center B cell differentiation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36279432.
- Also identified by DOI 10.1073/pnas.2215921119 and PMC identifier 9636909.
- Licence recorded as CC BY-NC-ND.
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Abstract
Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA<sup>+</sup> 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 a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN.
Medical subject headings
- Glomerulonephritis, IGA