Toll-like receptor and interleukin-1 receptor regulator (TILRR) (TILRR)

Toll-like receptor and interleukin-1 receptor regulator (TILRR) is a potent modulator of the innate immune response, functioning as a co-receptor for the Interleukin-1 receptor type 1 (IL-1R1) and various Toll-like receptors (TLRs), including TLR4 [1, 2]. It is a truncated splice variant of the FREM1 gene and is primarily localized to the cell surface and extracellular space [3, 4]. TILRR significantly amplifies inflammatory signaling by enhancing the recruitment of key adapter proteins, such as MyD88 and IRAK1, to the receptor complex, thereby lowering the threshold for NF-kappaB and MAPK pathway activation [1, 3]. This amplification leads to a robust increase in the production of pro-inflammatory cytokines and adhesion molecules [2]. Because of its central role in magnifying the inflammatory cascade, TILRR is strongly associated with the pathogenesis of chronic inflammatory diseases, including atherosclerosis, rheumatoid arthritis, and ischemic stroke [2, 3]. Therapeutic interest in TILRR stems from its potential as a target for site-specific anti-inflammatory drugs that could modulate IL-1 and TLR signaling without the broad immunosuppressive effects of total receptor blockade [1, 2]. Current research is focused on developing monoclonal antibodies and synthetic peptides designed to disrupt the interaction between TILRR and its primary receptor complexes [1, 3]. References: [1] Zhang et al. (2011) J Biol Chem 286(7):5341-51; [2] Collis et al. (2017) Sci Rep 7(1):13669; [3] Al-Logmani et al. (2016) J Immunol 196(12):5109-20; [4] UniProt Q5H8C1.

Other names

FREM1 isoform 2Fras1-related extracellular matrix protein 1 isoform 2IL-1R1/TLR co-receptorToll-like receptor and interleukin-1 receptor regulator

TILRR acts as a co-receptor that binds to the IL-1R1 and TLR complexes, facilitating the recruitment of the adapter protein MyD88 and the kinase IRAK1. This interaction lowers the threshold for activation and amplifies the downstream signaling cascade, leading to enhanced NF-kappaB and MAPK-mediated inflammatory gene expression [1, 3].