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

• DOI: 10.1126/sciimmunol.abk0182
• Publication Date: 2022-01-21
• Authors: Margaret M. McDaniel; Amanpreet Singh C...; Aakanksha Jain; Hannah E. Meibers; Irene Saha; Yajing Gao; Viral G. Jain; Krishna M. Roskin; Sing Sing Way; Chandrashekhar Pa...
• Keywords: Proinflammatory cytokine; Cytokine Storm; Innate lymphoid cell

Cytokine storm and sterile inflammation are common features of T cell-mediated autoimmune diseases 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 cells (TEM) to mobilize broad proinflammatory program in immune system. Cognate interactions between TEM myeloid led induction an transcriptional profile was reminiscent, yet entirely independent, classical pattern recognition receptor (PRR) activation. This PRR-independent "de novo" driven preexisting engagement both CD40 tumor necrosis factor (TNFR) on cells. toxicity pathology could be completely rescued ablating these pathways genetically or pharmacologically multiple models cell-driven inflammation, indicating instruction system primary driver associated immunopathology. Thus, previously unknown trigger amenable therapeutic interventions.