The integrated stress response pathway controls cytokine production in tissue-resident memory CD4⁺ T cells.

ABSTRACT: Tissue-resident memory T (T_RM) cells are a specialized T cell population that reside in tissues and provide a rapid protective response upon activation. Here, we showed that human and mouse CD4⁺ T_RM cells existed in a poised state and stored messenger RNAs encoding proinflammatory cytokines without protein production. At steady state, cytokine mRNA translation in T_RM cells was suppressed by the integrated stress response (ISR) pathway. Upon activation, the central ISR regulator, eIF2α, was dephosphorylated and stored cytokine mRNA was translated for immediate cytokine production. Genetic or pharmacological activation of the ISR-eIF2α pathway reduced cytokine production and ameliorated autoimmune kidney disease in mice. Consistent with these resul

SUBMITTER: Asada N 

PROVIDER: S-EPMC11957990 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature