Neutrophil Irg1/itaconate axis protects against experimental colitis by suppressing local inflammation and maintaining hematopoietic homeostasis.

ABSTRACT: Inflammatory bowel disease (IBD) is a chronic, relapsing disorder characterized by excessive inflammation and often associated with extraintestinal symptoms. Current treatments remain unsatisfactory. Although immune response gene 1 (Irg1) and its product itaconate show promise in alleviating experimental colitis, the underlying mechanisms are unclear. Here, we describe an endogenous, homeostatic pattern that controls both local and systemic inflammatory responses in experimental murine colitis. Our study identifies neutrophils in inflamed colon as the primary Irg1 source. Irg1 deficiency worsens disease severity, as shown by greater weight loss, higher disease activity index, shorter colon length, more severe tissue damage, and more neutrophil infiltration. Depleting neutrophils with Ly6G

SUBMITTER: Zhao N 

PROVIDER: S-EPMC12717350 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature