CCDC134 controls TLR biogenesis through the ER chaperone Gp96.

ABSTRACT: Toll-like receptors (TLRs) are central to initiate immune responses against invading pathogens. To ensure host defense while avoiding aberrant activation leading to pathogenic inflammation and autoimmune diseases, TLRs are tightly controlled by multilevel regulatory mechanisms. Through a loss-of-function genetic screen in a reporter cell line engineered to undergo cell death upon TLR7-induced IRF5 activation, we identified here CCDC134 as an essential factor for TLR responses. CCDC134 deficiency impaired endolysosomal TLR-induced NF-κB, MAPK, and IRF5 activation, as well as downstream production of proinflammatory cytokines and type I interferons. We further demonstrated that CCDC134 is an endoplasmic reticulum (ER)-resident interactor of Gp96 (HSP90B1/Grp94), an ER chaperone essential for

SUBMITTER: Bernaleau L 

PROVIDER: S-EPMC11629888 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature