Document Detail

Different roles of TiR8/Sigirr on toll-like receptor signaling in intrarenal antigen-presenting cells and tubular epithelial cells.
MedLine Citation:
PMID:  17495864     Owner:  NLM     Status:  MEDLINE    
Toll-like receptors (TLRs) exist on both myeloid and intrinsic renal cells contributing to the initiation of innate immunity during renal infection with uropathogenic Escherichia coli. Toll-interleukin 1 receptor (IL-1R) (TIR)8/SIGIRR is an orphan receptor of the TLR/IL-1R family, which suppresses TLR signaling of immune cells and is highly expressed in the kidney. Lack of TIR8/SIGIRR is associated with enhanced renal chemokine signaling upon exposure to lipopolysaccharide (LPS). This was because of TIR8/SIGIRR expression on resident intrarenal myeloid cells rather than tubular epithelial cells which express it on basolateral and luminal membranes. The lack of TIR8/SIGIRR does not enhance TLR/IL-1R signaling in tubular epithelial cells as was observed in monocytes. TIR8/SIGIRR is induced in monocytes treated with LPS or tumor necrosis factor and interferon-gamma in a dose-dependent manner but was downregulated in treated tubule epithelial cells. This cell type-specific regulation and function did not relate to mRNA splice variants but was associated with N- and O-glycosylation of the receptor in renal cells of myeloid and nonmyeloid origin. Our studies show that resident myeloid cells contribute to TLR-mediated antimicrobial immunity in the kidney and that this function is controlled by Tir8/sigirr. TIR8/SIGIRR does not suppress TLR signaling in tubular epithelial cells, which supports their role as sensors of microbial infection in the kidney.
M Lech; C Garlanda; A Mantovani; C J Kirschning; D Schlöndorff; H-J Anders
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-02
Journal Detail:
Title:  Kidney international     Volume:  72     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-12     Completed Date:  2007-09-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  182-92     Citation Subset:  IM    
Nephrological Center, Medical Policlinic, University of Munich, Munich, Germany.
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MeSH Terms
Antigen-Presenting Cells / immunology,  metabolism*
Cells, Cultured
Epithelial Cells / immunology,  metabolism*
Immunity, Innate
Kidney / cytology*,  immunology
Lipopolysaccharides / pharmacology
Mice, Knockout
Myeloid Cells
Receptors, Interleukin-1 / immunology,  physiology*
Signal Transduction / immunology
Toll-Like Receptors / immunology,  metabolism*
Reg. No./Substance:
0/Lipopolysaccharides; 0/Receptors, Interleukin-1; 0/Tir8 protein, mouse; 0/Toll-Like Receptors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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