Joao Vinicius Honorio da Silva, MS: No financial relationships to disclose
Introduction/Rationale: 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.
