Sex-Related Differences in the Morphology and Subpopulation Composition of Colon Lymphocytes in Experimental Acute Colitis

Abstract

Morphological manifestations of acute colitis and subpopulation composition of colon lymphocytes were studied in male and female C57Bl/6 mice with acute dextran-induced colitis. We evaluated the severity of colitis symptoms, morphological changes in the colon, and prevalence of epithelialized and non-epithelialized ulcers. The subpopulation composition of lymphocytes (CD3-CD19 B cells, CD3CD4 T helpers, CD3CD8 cytotoxic T cells, and CD4CD25FOXP3 regulatory T cells) was assessed by flow cytofluorometry in suspension of colon cells prepared by enzymatic disintegration. In males, clinical manifestations of acute colitis and morphological changes were more severe and the prevalence of non-epithelialized ulcers was higher than in females. In females, the content of T, B, and regulatory T cells in the colon wall was higher, while the content of cytotoxic T cells was lower than in males. In females with acute colitis, the absolute lymphocyte count and the content of B cells and regulatory T cells decreased, while the percentage of cytotoxic T cells increased in comparison with intact animals. In males with acute colitis, the levels of regulatory T and B cells increased in comparison with the corresponding parameter in intact animals. Morphological changes and changes in the lymphocyte subpopulations, detected in males and females with acute colitis, were determined by different levels of sex steroid hormones.

Experimental colitis promotes sustained, sex-dependent, T-cell-associated neuroinflammation and parkinsonian neuropathology

“…Despite similar DAI scores, the inflammatory effects of DSS were somewhat blunted in females, with no significant difference in Ptprc and DSS-induced increases in Cd8b and Snca only in RGS10 −/− mice. This is in keeping with reports that female mice are less sensitive to DSS colitis [ 72 ], and it may have contributed to limited observation of colitis-related neuropathology in female mice in our study. Our random forest model emphasized that colitis impacted TH + dopaminergic neurons in males much more than female mice but also that the severity of colitis as reflected by the DAI score was a substantially better predictor of striatal TH levels than was the binary classification of DSS or H2O treatment.…”

“…This study identified significant increases in Cd8b and Ifng expression in the SNpc of DSS-treated males, and in males, these variables were ranked as the most highly associated with striatal TH levels after MPTP. DSS colitis models induce accumulation of CD8 + T-cells in the colon, particularly in male mice [ 72 ]. Indeed, this study found increased Cd8b expression in colon tissue of male mice following acute colitis but more modest changes in females which only reached statistical significance in females lacking RGS10.…”

Sex differences in pain-related behaviors and clinical progression of disease in mouse models of visceral pain

“…Consistent with previous studies [2,10,39], 2.5% DSS treatment in drinking water resulted in increases in DAI scores in both males and females in a time-dependent manner, with higher DAI scores as the days of treatment progressed. As expected, DAI scores in DSS-treated male and female mice were significantly (p < 0.0001) higher than scores in their respective water controls, validating that DSS treatment induces a symptom profile consistent with colitis in both sexes (Figure 3C).…”

The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis

“…This gender dependent dimorphism of EBI2 −/ − IL10 −/− animals has parallels in the literature. Other sexual dimorphisms regarding colitis severity have been related to various factors including microbiota 37 and colon cellular infiltrate 38 or direct of effects of estradiol. 39 Further, in a recent study with the murine TNF ΔARE model, protection from ileitis was observed in male, but not female mice with a specific pathogenfree flora.…”