| Negative Regulation of Signaling by a Soluble Form of Toll-Like Receptor 9. | |
| | |
MedLine Citation:
|
PMID: 21604257 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Nucleic acids structures are highly conserved through evolution and when self nucleic acids are aberrantly detected by Toll-Like Receptors (TLRs) they contribute to autoimmune disease. For this reason, multiple regulatory mechanisms exist to prevent response to self nucleic acids. TLR9 is a nucleic acid sensing TLR that is regulated at multiple levels including association with accessory proteins, intracellular localization and proteolytic processing. In the endolysosomal compartment TLR9 is proteolytically processed to an 80 kilodalton form (p80) and this processing is a prerequisite for activation. Here we identified a soluble form of TLR9 generated by a novel proteolytic event that cleaved TLR9 between amino acids 724-735. Similar to p80, sTLR9 was generated in endosomes. However, generation of sTLR9 was independent of the cysteine protease cathepsin B active at acidic pH, but partially dependent on cathepsin S, a protease active at neutral pH. Most importantly, sTLR9 inhibited TLR9-dependent signaling. Together, these data support a model where an intrinsic proteolytic processing mechanism negatively regulates TLR9 signaling. Proper balance between the independent proteolytic events likely contributes to regulation of TLR9 mediated innate immunity and prevention of autoimmune disease. |
| | |
Authors:
|
Annapoorani Chockalingam; Jody L Cameron; James C Brooks; Cynthia A Leifer |
Related Documents
:
|
21666027 - In vitro fermentation of linear and alpha-1,2-branched dextrans by the human fecal micr... 16658077 - Meristematic activity during adventitious root primordium development: influences of en... 5573727 - Ribosomal competence and spore germination in fusarium solani. 18787817 - Investigating the effect of patulin, penicillic acid and edta on biofilm formation of i... 18054427 - Biodegradability enhancement of purified terephthalic acid wastewater by coagulation-fl... 17234417 - Discovery of anticonvulsant activity of abietic acid through application of linear disc... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-5-23 |
Journal Detail:
|
Title: European journal of immunology Volume: - ISSN: 1521-4141 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-5-23 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
|
Department of Microbiology and Immunology, College of Veterinary Medicine, VMC C5-153, Cornell University, Ithaca 14853, NY. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Modelling the effect of venous disease on quality of life.
Next Document: Batf3 transcription factor-dependent DC subsets in murine CMV infection: differential impact on T ce...