TREML4 adds fuel to the TLR7 fire

Abstract T Toll-like receptor TLR7 recognizes nucleic acids and is thought to have a key role in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). In this issue of Nature Immunology, RamirezOrtiz et al. demonstrate that the receptor TREML4 amplifies TLR7-induced signaling and type I interferon responses by recruiting TLR7 and the adaptor Myd88 to the endolysosomal compartment, which subsequently leads to activation of the mitogen-activated protein kinase p38 and phosphorylation of the transcription factor STAT1 (ref. 1). Furthermore, the authors show that TREML4 deficiency results in amelioration of the development of SLE-like symptoms in lupus-prone MRL/lpr mice. SLE is a systemic autoimmune disorder that can affect the skin, joints, lungs and kidneys and the nervous system. Defects in the clearance of necrotic and apoptotic cells are thought to lead to the accumulation of self DNA and RNA that trigger the inflammation associated with this disease2. Single-stranded RNA is recognized by TLR7 in both humans and mice, whereas double-stranded DNA is recognized by TLR9. This process activates dendritic cells and, subsequently, T cells and B cells, which results in the production of autoantibodies that then form complexes with the self DNA and RNA. These complexes can be ingested by phagocytosis by dendritic cells via the receptor FcγRIIa and, in turn, trigger the production of type I interferon, which is thought to have a central role in the pathogenesis of SLE3. The importance of TLRs that recognize nucleic acids in the pathogenesis of SLE is underscored by the observation that lupus-prone MRL/lpr mice on a TLR7-deficient background have less severe disease than that of their TLR7-expressing counterparts4 and by the early onset of lupus in BXSB mice, which have a duplication of the TReML4 adds fuel to the TLR7 fire

DOI: 10.1038/ni.3149

1 Figure or Table

Cite this paper

@article{Netea2015TREML4AF, title={TREML4 adds fuel to the TLR7 fire}, author={Mihai G. Netea and Frank L. van de Veerdonk}, journal={Nature Immunology}, year={2015}, volume={16}, pages={445-446} }