Regional and Sex-Dependent Immune Profiling Across the Colon in A Mouse Model of Ulcerative Colitis.

Abstract

Ulcerative colitis (UC), an incurable inflammatory bowel disease, is characterized by a dysregulated immune system leading to mucosal damage along the large intestine. Sex-related differences in immune responses may influence the pathogenesis and disease course in UC. Given the distinctive immune profile across the gastrointestinal tract, determining how the immune system changes along the large intestine in healthy and disease conditions between sexes is critical for understanding UC pathophysiology. Here, we characterized the profile of immune cells and cytokines across segments (cecum, proximal, medial, and distal colon) of the large intestine collected from C57BL/6 male and female mice treated with 5% dextran sodium sulfate to induce colitis or water (healthy) using flow cytometry and Multiplex ELISA. Our study reveals that at steady states, females have a higher proportion of most myeloid and lymphoid cells than males, accompanied by a gradual increase in innate immune cells from the cecum to the distal colon in healthy females. Males had a higher level of several T helper 17 (TH17) cytokines in the medial and distal colon than females. Colitis was associated with increased granulocytes and tolerogenic immune cells in the medial and distal colon, and a shift in proinflammatory and TH17 cytokine levels toward the cecum in males. The immune profile differs along the large intestine between males and females at steady state and in colitic conditions, highlighting the importance of considering regional differences along the large intestine between sexes during diagnosis and while assessing the efficacy of new therapies using UC mouse models.