Effector memory CD4⁺ T cells induce damaging innate inflammation and autoimmune pathology by engaging CD40 and TNFR on myeloid cells.

ABSTRACT: Cytokine storm and sterile inflammation are common features of T cell-mediated autoimmune diseases and T cell-targeted cancer immunotherapies. Although blocking individual cytokines can mitigate some pathology, the upstream mechanisms governing overabundant innate inflammatory cytokine production remain unknown. Here, we have identified a critical signaling node that is engaged by effector memory T cells (T_EM) to mobilize a broad proinflammatory program in the innate immune system. Cognate interactions between T_EM and myeloid cells led to induction of an inflammatory transcriptional profile that was reminiscent, yet entirely independent, of classical pattern recognition receptor (PRR) activation. This PRR-independent "de novo" inflammation was driven by preexisting T<

SUBMITTER: McDaniel MM 

PROVIDER: S-EPMC9036191 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature