论文部分内容阅读
UNC93B1存在于内质网上,具多次跨膜区域,它能与TLR(Toll-like receptors,TLRs)-3,-7,-9发生特异性结合并将它们从内质网上运输(trafficking)至溶酶体中。UNC93B1与TLRs相互作用并通过MyD88/TRIF途径进行着信号传递。TLRs通过识别相应的高度保守的病原相关分子模式(PAMPs),在介导防御外来微生物入侵的先天性免疫反应并桥连或触发获得性免疫反应中起重要作用。在3d(N-乙基-N-亚硝基脲诱导的染色体基因的隐性突变)小鼠中,UNC93B1上H412R位点的突变阻断了其和TLRs的结合,进而阻碍了TLRs信号的传递,这使得该小鼠易被各种病原体感染。另外,UNC93B1的突变阻止了小鼠体内抗原的交叉呈递途径,也降低了MHC-II类分子呈递途径。UNC93B1缺陷使得人体易受单纯疱疹病毒I型(HSV-1)病毒感染而引起单纯疱疹病毒1型脑炎(HSE)。此外,通过调节UNC93B1和TLR7/9的接触可控制或避免系统性红斑狼疮、关节炎等自身性免疫疾病的发生。
UNC93B1 is present in the endoplasmic reticulum and has multiple transmembrane domains that specifically bind to TLRs -3, -7, and -9 and trafficking them from the endoplasmic reticulum to Lysosomes. UNC93B1 interacts with TLRs and signals through the MyD88 / TRIF pathway. TLRs play an important role in mediating the innate immune response against foreign microbial intrusion and bridging or triggering an adaptive immune response by recognizing the corresponding highly conserved pathogen-associated molecular patterns (PAMPs). In the 3d (N-ethyl-N-nitrosourea-induced recessive mutation of chromosomal genes) mice, mutations in the H412R site on UNC93B1 blocked its binding to TLRs and prevented the delivery of TLRs signals , Which makes the mouse susceptible to various pathogens. In addition, mutations in UNC93B1 prevent cross-presentation of antigens in mice and also decrease MHC-II class molecule presentation. UNC93B1 deficiency causes the human body to become susceptible to herpes simplex virus type 1 (HSV-1) virus causing herpes simplex virus type 1 encephalitis (HSE). In addition, the occurrence of autoimmune diseases such as systemic lupus erythematosus, arthritis and the like can be controlled or prevented by adjusting the contact between UNC93B1 and TLR7 / 9.