Non-hematopoietic STAT6 induces epithelial tight junction dysfunction and promotes intestinal inflammation and tumorigenesis

Sep 20, 2019Mucosal immunology

STAT6 outside blood cells disrupts gut lining, leading to inflammation and tumor growth

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Abstract

STAT6 activation was detected in inflamed colonic epithelium of active IBD patients.

  • Non-hematopoietic STAT6 triggered DSS-induced colitis and tumor development.
  • STAT6 may enhance gut permeability and microbiota translocation by disrupting epithelial tight junctions.
  • Long-myosin light-chain kinase (MLCK1) is a target of STAT6 that contributes to tight junction dysfunction.
  • Neutralization of IL-13 improved gut permeability and reduced DSS-induced colitis by inhibiting epithelial STAT6 activation.
  • Pharmacological inhibition of STAT6 reduced intestinal tumor formation in mice.
  • Tumoral p-STAT6 levels are positively correlated with clinical stage and poor prognosis in human colorectal cancer.

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