Unc93B1 Restricts Systemic Lethal Inflammation by Orchestrating Toll-like Receptor 7 and 9 Trafficking

被引：175

作者：

Fukui, Ryutaro ^{[1
]}

Saitoh, Shin-Ichiroh ^{[1
]}

Kanno, Atsuo ^{[1
]}

Onji, Masahiro ^{[1
]}

Shibata, Takuma ^{[1
,2
]}

Ito, Akihiko ^{[4
]}

Onji, Morikazu ^{[5
]}

Matsumoto, Mitsuru ^{[6
]}

Akira, Shizuo ^{[7
,8
]}

Yoshida, Nobuaki ^{[3
]}

Miyake, Kensuke ^{[1
,2
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Div Infect Genet, Dept Microbiol & Immunol,Minato Ku, Tokyo 1088639, Japan

[2] Univ Tokyo, Inst Med Sci, Lab Innate Immun, Minato Ku, Tokyo 1088639, Japan

[3] Univ Tokyo, Inst Med Sci, Lab Dev Genet, Ctr Expt Med & Syst Biol,Minato Ku, Tokyo 1088639, Japan

[4] Kinki Univ, Dept Pathol, Fac Med, Osaka 5898511, Japan

[5] Ehime Univ, Dept Gastroenterol & Metabol, Grad Sch Med, Matsuyama, Ehime 7910295, Japan

[6] Univ Tokushima, Div Mol Immunol, Inst Enzyme Res, Tokushima 7708504, Japan

[7] World Premier Int Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan

[8] Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan

来源：

IMMUNITY | 2011年 / 35卷 / 01期

关键词：

DENDRITIC CELLS; B-CELLS; LUPUS-ERYTHEMATOSUS; ANTIMICROBIAL PEPTIDE; AUTOIMMUNE-DISEASES; BLOOD-COAGULATION; BACTERIAL-DNA; MURINE LUPUS; I INTERFERON; CPG MOTIFS;

D O I：

10.1016/j.immuni.2011.05.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Toll-like receptor-7 (TLR7) and 9, innate immune sensors for microbial RNA or DNA, have been implicated in autoimmunity. Upon activation, TLR7 and 9 are transported from the endoplasmic reticulum (ER) to endolysosomes for nucleic acid sensing by an ER-resident protein, Unc93B1. Little is known, however, about a role for sensor transportation in controlling autoimmunity. TLR9 competes with TLR7 for Unc93B1-dependent trafficking and predominates over TLR7. TLR9 skewing is actively maintained by Unc93B1 and reversed to TLR7 if Unc93B1 loses preferential binding via a D34A mutation. We here demonstrate that mice harboring a D34A mutation showed TLR7-dependent, systemic lethal inflammation. CD4(+) T cells showed marked differentiation toward T helper 1 (Th1) or Th17 cell subsets. B cell depletion abolished T cell differentiation and systemic inflammation. Thus, Unc93B1 controls homeostatic TLR7 activation by balancing TLR9 to TLR7 trafficking.

引用

页码：69 / 81

页数：13

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[21] Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing [J].