CD177⁺ neutrophils as functionally activated neutrophils negatively regulate IBD

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Neutrophils infiltrate inflamed mucosa in inflammatory bowel disease (IBD), contributing to pathogenesis.
• CD177 is a specific marker for neutrophils, upregulated during inflammation, but its role in IBD pathogenesis is unclear.

Purpose of the Study:

• To investigate the role and function of CD177-expressing neutrophils (CD177⁺ neutrophils) in the pathogenesis of inflammatory bowel disease (IBD).

Main Methods:

• Quantitative RT-PCR, flow cytometry, and immunohistochemistry were used to analyze CD177 expression in IBD patients.
• RNA sequencing compared gene expression between CD177⁺ and CD177^- neutrophils.
• CD177 knockout (CD177^-/-) and wild-type mice were used to model colitis.

Main Results:

• CD177⁺ neutrophils were significantly elevated in peripheral blood and inflamed mucosa of active IBD patients.
• CD177⁺ neutrophils exhibited enhanced bactericidal activity and produced higher levels of IL-22 and TGF-β, with lower pro-inflammatory cytokines.
• CD177^-/- mice showed more severe colitis, impaired intestinal barrier, and reduced IL-22 production.

Conclusions:

• CD177⁺ neutrophils are a functionally activated subset with a protective role in IBD via enhanced bacterial defense and IL-22 production.
• Targeting CD177⁺ neutrophils may offer a therapeutic strategy for IBD treatment.