SCIMP is a universal Toll-like receptor adaptor in macrophages.

We report here that SCIMP is phosphorylated and activated in response to agonists of multiple TLRs, including TLR2, TLR3, TLR4, and TLR9. SCIMP also interacts with TLRs that are known to signal from both the cell surface and endosomal compartments. In so doing, this transmembrane adaptor presents Lyn, along with other effectors such as Grb2, Csk, and SLP65, to multiple TLRs during cellular activation. CRISPR-mediated knockout or silencing of SCIMP in macrophages alters TLR signaling outputs and the production of IL-6 and IL-12p40 downstream of multiple TLRs, and upon challenge with live bacteria. Furthermore, the selectivity in cytokine responses is preserved downstream of TLR3, with inducible expression of Il-12p40 and IL-6, but not IFNβ, being SCIMP dependent. SCIMP is thus a universal TLR adaptor for scaffolding the Lyn tyrosine kinase and its effectors to enable responses against a wide range of danger signals.
PMID: 31468585 [PubMed - as supplied by publisher]

Source: Journal of Leukocyte Biology - August 28, 2019 Category: Hematology Authors: Luo L, Curson JEB, Liu L, Wall AA, Tuladhar N, Lucas RM, Sweet MJ, Stow JL Tags: J Leukoc Biol Source Type: research