Slc6a13 deficiency promotes Th17 responses during intestinal bacterial infection.

Abstract:

:The γ-amino butyric acid (GABA)ergic system shapes the activation and function of immune cells. The present study was conducted to explore the regulation of GABA transporter (GAT)-2 on the differentiation of Th17 cells. Here we found that Th17 cells show higher abundance of GAT-2, and have distinct cellular metabolic signatures, such as the GABA shunt pathway, as compared to naïve T cells. GAT-2 deficiency had little effect on the metabolic signature in naïve T cells, but impaired the GABA uptake and GABA shunt pathway in Th17 cells. GAT-2 deficiency had little effect on T cell development and peripheral T cell homeostasis; however, its deficiency promoted Th17 cell differentiation in vitro. Mechanistically, GAT-2 deficiency promoted differentiation of Th17 cells through activation of GABA-mTOR signaling. In a mouse model of intestinal infection and inflammation, GAT-2 deficiency promoted Th17 responses. Collectively, GAT-2 deficiency promotes Th17 cell responses through activation of GABA-mTOR signaling.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Ren W,Liao Y,Ding X,Jiang Y,Yan J,Xia Y,Tan B,Lin Z,Duan J,Jia X,Yang G,Deng J,Zhu C,Hardwidge PR,Li J,Zhu G,Yin Y

doi

10.1038/s41385-018-0111-7

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

531-544

issue

2

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-018-0111-7

journal_volume

12

pub_type

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