Open AccessTGF ‐β1 improves mucosal IgA dysfunction and dysbiosis following intestinal ischaemia–reperfusion in mice
Author(s) -
Zhang XuYu,
Liu ZiMeng,
Zhang HuFei,
Li YunSheng,
Wen ShiHong,
Shen JianTong,
Huang WenQi,
Liu KeXuan
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12789
Subject(s) - immunoglobulin a , smad , dysbiosis , immunology , transforming growth factor , intestinal mucosa , superior mesenteric artery , cytokine , immune system , biology , mucosal immunology , intestinal villus , endocrinology , medicine , small intestine , immunity , gut flora , immunoglobulin g
Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor ( TGF )‐β1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF ‐β1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF ‐β1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF ‐β1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR ), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria‐binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor‐β1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF ‐β1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB ‐431542, a specific inhibitor of activating mothers against decapentaplegic homologue ( SMAD ) 2/3, totally blocked the inductive effect of TGF ‐β1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF ‐β1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF ‐β receptor 1/ SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF ‐β1.