G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation

Christian Sina1, Olga Gavrilova, Matti Förster

  • 1Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany.

Insights

G protein-coupled receptor 43 (GPR43) plays a dual role in intestinal inflammation. While essential for recruiting neutrophils to fight infection, it also contributes to tissue damage in chronic conditions.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Neutrophilic granulocytes (polymorphonuclear leukocytes, PMNs) are crucial for combating infection.
  • G protein-coupled receptor 43 (GPR43), which binds propionate and butyrate, is highly expressed on PMNs.
  • The in vivo function of GPR43 in immune responses remains largely undefined.

Purpose of the Study:

  • To investigate the role of GPR43 in dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammation.
  • To elucidate the molecular mechanisms underlying GPR43-mediated PMN migration.

Main Methods:

  • Utilized wild-type and Gpr43-deficient mice in DSS-induced colitis models.
  • Assessed colonic inflammation severity through clinical signs, histology, and cytokine analysis.
  • Evaluated PMN chemotaxis ex vivo using transwell assays and analyzed signaling pathways.

Main Results:

  • Gpr43(-/-) mice exhibited increased mortality and reduced PMN invasion in acute DSS colitis.
  • In chronic DSS colitis, Gpr43(-/-) mice showed decreased PMN migration but were protected from tissue damage.
  • GPR43-mediated PMN migration involved p38alpha kinase and keratinocyte chemoattractant, and affected L-selectin shedding.

Conclusions:

  • GPR43 is critical for recruiting PMNs to control bacterial translocation in the gut.
  • PMNs, via GPR43, have a bipotential role, contributing to both host defense and tissue destruction in chronic inflammation.

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