title: Identification and characterization of a unique leucine-rich repeat protein (LRRC33) that inhibits Toll-like receptor-mediated NF-κB activation.
abstract: Toll-like receptors (TLRs) are important initiators in innate immune responses against pathogenic microbes such as viruses, intracellular bacteria or parasites. Although the innate immune system is designed to fight infectious pathogens, excessive activation of TLR signaling may lead to unwarranted inflammation with hazardous outcomes. Mechanisms of restraining excessive inflammation and controlling homeostasis for innate immunity are the focus of intense study. Here we showed that LRRC33, a novel member of leucine-rich repeat (LRR) protein family, plays a critical role in desensitizing TLR signaling. LRRC33 is TLR homolog that contains 17 putative LRRs in the extracellular region but lacks a cytoplasmic Toll/IL-1 receptor (TIR) domain. Expression of LRRC33 appears to be ubiquitous with high level of expression found in bone marrow, thymus, liver, lung, intestine and spleen. The LRRs of LRRC33 is required for the interaction with TLR and its inhibitory effect on NF-κB and AP-1 activation as well as cytokine production. Our study sheds new insight into the TLR signaling and inflammatory response in development and human diseases.
authors.affiliation: Department of Immunology, Nankai University School of Medicine, Nankai University, Nankai District, Weijing Road No. 94, Tianjin 300071, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Limin
authors.initials: L
authors.lastname: Chai
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Che
authors.forename: Siping
authors.initials: S
authors.lastname: Min
authors.forename: Rongcun
authors.initials: R
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D053779:Latent TGF-beta Binding Proteins; D000090263:Leucine-Rich Repeat Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D058261:Receptor Activity-Modifying Proteins; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D020298:U937 Cells
chemical_list: D002352:Carrier Proteins; D053779:Latent TGF-beta Binding Proteins; D000090263:Leucine-Rich Repeat Proteins; D016328:NF-kappa B; C582014:NRROS protein, human; D011506:Proteins; D058261:Receptor Activity-Modifying Proteins; D051193:Toll-Like Receptors