T-cell function is critical for murine cholesterol gallstone formation.

Area of Science:

• Immunology
• Gastroenterology
• Pathogenesis of Gallstones

Background:

• Cholesterol gallstone formation is multifactorial, influenced by genetic and environmental factors.
• Gallbladder inflammation is often observed during gallstone development, but the role of the immune system remains unclear.

Purpose of the Study:

• To investigate the role of adaptive immunity in cholesterol gallstone formation.
• To identify specific immune cell subsets involved in cholelithogenesis.
• To characterize the inflammatory response during gallstone development.

Main Methods:

• Utilized immunocompetent and immunodeficient (Rag2(-/-)) mice, with and without Helicobacter spp. infection.
• Performed lymphocyte transfer studies (splenocytes, T cells, B cells) to assess their role in gallstone formation.
• Quantified gallbladder inflammation and gene expression related to mucin and inflammatory pathways.

Main Results:

• Wild-type mice had significantly higher cholesterol gallstone prevalence than Rag mice.
• Helicobacter spp. infection increased gallstone prevalence in immunocompetent mice.
• Transfer of T cells, but not B cells, to Rag2(-/-) mice markedly increased gallstone prevalence.
• Adaptive immunity upregulated gallbladder mucin production and induced pro-inflammatory gene expression.

Conclusions:

• T cells are critical mediators of cholesterol gallstone formation in mice.
• Cholesterol crystals induce pro-inflammatory cytokine expression in a T-cell-dependent manner.
• Acquired immunity and inflammation are key factors in cholesterol gallstone pathogenesis.