T cells and their immunometabolism: A novel way to understanding sepsis immunopathogenesis and future therapeutics

Abstract

Sepsis has always been considered as a big challenge for pharmaceutical companies in terms of discovering and designing new therapeutics. The pathogenesis of sepsis involves aberrant activation of innate immune cells (i.e. macrophages, neutrophils etc.) at early stages. However, a stage of immunosuppression is also observed during sepsis even in the patients who have recovered from it. This stage of immunosuppression is observed due to the loss of conventional (i.e. CD4⁺, CD8⁺) T cells, Th17 cells and an upregulation of regulatory T cells (Tregs). This process also impacts metabolic processes controlling immune cell metabolism called immunometabolism. The present review is focused on the T cell-mediated immune response, their immunometabolism and targeting T cell immunometabolism during sepsis as future therapeutic approach. The first part of the manuscripts describes an impact of sepsis on conventional T cells, Th17 cells and Tregs along with their impact on sepsis. The subsequent section further describes the immunometabolism of these cells (CD4⁺, CD8⁺, Th17, and Tregs) under normal conditions and during sepsis-induced immunosuppression. The article ends with the therapeutic targeting of T cell immunometabolism (both conventional T cells and Tregs) during sepsis as a future immunomodulatory approach for its management.

Keywords: Immunometabolism; Immunosuppression; Sepsis; T cells; Tregs.