We are thrilled to announce the latest publication of our lab, now published in the Journal of Experimental Medicine!

In this work, our amazing PhD student Léa Bernaleau studied how is TLR biogenesis controlled, discovering how CCDC134 controls TLR biogenesis through the ER-chaperone Gp96.

TLRs are key innate immune receptors which detect pathogens and initiate inflammatory responses, but can also trigger autoimmunity when disregulated.

Léa did a CRISPR/Cas9 loss-of-function screen in cells engineered tp die upon TLR7-induced IRF5 activation, and identified CCDC134 as an essential factor for TLR response.

CCDC134 deficiency impaired the folding, maturation and trafficking of TLRs, resulting in blunted inflammatory responses upon stimulation. We further discovered that CCDC134 does this by controlling the stability of the endoplasmic reticulum (ER)-resident Gp96 chaperone. Indeed, without CCDC134, Gp96 is hyperglycosylated and undergoes #ERAD degradation, so TLRs cannot be well-folded nor traffic to their corresponding membranes for pathogen detection and signalling.

This work was performed thanks to SNSF funding, the collaboration with Olivia Majer group at Max Planck Institute for Infection Biology and the support of our colleagues at Department of Immunobiology at UNIL.

Citation: Léa Bernaleau, Michaela Drobek, Fenja Blank, Philipp Walch, Maeva Delacrétaz, Ales Drobek, Marta Monguió-Tortajada, Petr Broz, Olivia Majer, Manuele Rebsamen; CCDC134 controls TLR biogenesis through the ER chaperone Gp96. J Exp Med 3 March 2025; 222 (3): e20240825. doi: https://doi.org/10.1084/jem.20240825