Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis

Area of Science:

• Immunology
• Gastroenterology

Background:

• The complement system is implicated in inflammatory bowel disease (IBD) pathogenesis.
• The specific role of the membrane attack complex (MAC) in IBD development remains unclear.

Purpose of the Study:

• To investigate the role of MAC in dextran sulfate sodium (DSS)-induced acute colitis.
• To determine if MAC has a protective or detrimental effect in this IBD model.

Main Methods:

• Utilized C6-deficient mice, which cannot form MAC, to model acute colitis via DSS administration.
• Compared disease severity in C6-deficient mice versus wild-type (WT) mice.
• Administered exogenous C6 to C6-deficient mice to assess its therapeutic effect.

Main Results:

• DSS-induced colitis was significantly aggravated in C6-deficient mice, showing greater weight loss, higher disease activity index (DAI), and more severe colon damage.
• Histological analysis revealed increased epithelial ulcerations and leukocyte infiltration with higher myeloperoxidase (MPO) levels in C6-deficient mice.
• Exogenous C6 administration ameliorated colitis in C6-deficient mice, and elevated pro-inflammatory mediators (IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1, IL-17F) were observed in these mice.

Conclusions:

• The membrane attack complex (MAC) plays a protective role in acute colitis.
• MAC contributes to host defense mechanisms in the context of inflammatory bowel disease.
• Blocking MAC exacerbates colitis, suggesting its importance in mitigating intestinal inflammation.