Atypical Mitochondrial Phenotype of Colonic CD4+ and CD8+ T Cells During Experimental Chronic Colitis

Abstract

Background: Patients with ulcerative colitis (UC) suffer from a chronic relapsing-remitting inflammatory bowel disease and show heterogeneous disease severity and therapy response. It was recently reported that rectal biopsies from patients with UC show a downregulation of various mitochondrial genes during active UC. Methods: We used dextran sulfate sodium (DSS)-induced colitis as a preclinical mouse model for UC to study metabolic characteristics of ex vivo colonic lamina propria CD4+ and CD8+ T cells, B cells, eosinophils, neutrophils and intestinal epithelial cells during experimental acute and chronic inflammatory bowel disease and remission state. Results: Our results indicate that CD4+ and CD8+ T cells in the colon produce significantly less mitochondrial reactive oxygen species and possess smaller mitochondria during chronic DSS-induced colitis, which is resolved during remission state. In addition, CD4+ and CD8+ T cells exhibit increased glucose uptake during acute but defective glucose consumption during chronic DSS colitis. Conclusions: Together, our data provide evidence for an atypical mitochondrial phenotype of colonic CD4+ and CD8+ T cells during chronic colitis that is resolved during the remission phase of the disease.