| Unc93B1 Restricts Systemic Lethal Inflammation by Orchestrating Toll-like Receptor 7 and 9 Trafficking. | |
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MedLine Citation:
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PMID: 21683627 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ryutaro Fukui; Shin-Ichiroh Saitoh; Atsuo Kanno; Masahiro Onji; Takuma Shibata; Akihiko Ito; Morikazu Onji; Mitsuru Matsumoto; Shizuo Akira; Nobuaki Yoshida; Kensuke Miyake |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-15 |
Journal Detail:
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Title: Immunity Volume: - ISSN: 1097-4180 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Infectious Genetics, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108-8639, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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