Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis

Area of Science:

• Immunology
• Gastroenterology
• Inflammation Research

Background:

• Eosinophils are present in the colonic mucosa and increase during disease.
• Eosinophils are implicated in gastrointestinal (GI) inflammation pathogenesis.
• Eosinophils also regulate local immune responses and modulate tissue inflammation.

Purpose of the Study:

• To define the impact of eosinophils during acute phases of colitis in mice.
• To investigate the role of eosinophils in regulating immune responses and tissue inflammation in colitis.

Main Methods:

• Acute colitis was induced in C57BL/6J (control) or eosinophil-deficient (PHIL) mice using dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid, or oxazolone.
• Eosinophils were depleted using anti-interleukin (IL)-5 antibodies or bone marrow grafting from PHIL mice.
• Colon tissues were analyzed via immunohistochemistry, flow cytometry, reverse transcription PCR, and mass spectroscopy for lipid analysis.

Main Results:

• Eosinophil-deficient mice exhibited more severe colitis with increased neutrophil infiltration and elevated chemokines (CXCL1, CXCL2).
• Lipidomic analysis revealed a deficiency in the anti-inflammatory mediator 10, 17-dihydroxydocosahexaenoic acid (diHDoHE), specifically protectin D1 (PD1), in eosinophil-deficient mice.
• Exogenous PD1 administration reduced colitis severity, attenuated neutrophil infiltration, and decreased inflammatory markers (TNF-α, IL-1β, IL-6, iNOS) in mice. PD1 directly inhibited neutrophil transepithelial migration in vitro.

Conclusions:

• Eosinophils exert a protective effect in acute mouse colitis.
• This protection is mediated through the production of anti-inflammatory lipid mediators, such as protectin D1.