Influence of the absence of TRPM5 in CD4 T cells during the inflammatory response in autoimmune colitis induced by adoptive cell transfer 2258085

Abstract

Abstract Introduction Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, with an increased incidence in several countries. IBD is developed with the help of different leukocyte types, among which are CD4 T cells. It is known that the activation and differentiation of CD4 T cells is dependent on calcium. Since the transient receptor potential melastatin 5 channel (TRPM5) controls the concentration of intracellular calcium, we believe that this may influence the polarization and activation of CD4 T cells. Therefore, our hypothesis is that the selective absence of TRPM5 in CD4 T cells would result in greater susceptibility to intestinal inflammation, due to changes in their activation and differentiation. Methods For this, autoimmune colitis was induced by adoptive transfer of CD4+CD45RB+ T cells isolated from spleen and lymph nodes of WT or TRPM5 KO mice into Rag1 KO mice recipients (5 × 10⁵ cells i.p.). Mice were monitored for up to 7 weeks. Clinical, immunological and histological parameters were evaluated, and subjected to rigorous statistical analysis. Results Our results indicate that the absence of TRPM5 in CD4 T cells partially attenuated the severity of adoptive transfer—induced colitis, delaying the onset of clinical signs of the disease. Immunophenotyping of the colonic lamina propria revealed that mice receiving mice CD4+CD45RB+ T cells from TRPM5 KO mice showed a trend toward reduced CD69+CD4+ T cells, along with increased memory and PD-1+CD4+ T cells. A similar reduction in CD69+CD4+ T cells was also detected in the intestinal epithelium. These changes correlated with milder clinical symptoms, suggesting that TRPM5 contributes to CD4 T cell activation and proinflammatory responses during chronic colitis. Conclusion Therefore, TRPM5 plays an important role in CD4 T cells, and its absence may influence the activation and differentiation profile of these cells, prominently in the intestine, impacting the inflammatory response in colitis. Funding Source CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior); FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) Topic Categories Mucosal and Regional Immunology (MUC)