Document Detail

Signal inhibitory receptor on leukocytes-1 is a novel functional inhibitory immune receptor expressed on human phagocytes.
MedLine Citation:
PMID:  20375307     Owner:  NLM     Status:  MEDLINE    
Myeloid cells play a crucial role in controlling infection. Activation of these cells needs to be tightly regulated, because their potent effector functions can damage host tissue. Inhibitory receptors expressed by immune cells play an important role in restricting immune cell activation. In this study, we have characterized a hitherto unidentified ITIM-bearing receptor that is highly expressed on human neutrophils and monocytes: signal inhibitory receptor on leukocytes-1 (SIRL-1). The chromosomal location of SIRL-1 is adjacent to the human leukocyte receptor complex on chromosome 19q13.4 and contains two ITIMs in its cytoplasmic tail. As a classical ITIM-bearing receptor, SIRL-1 is capable of inhibiting FcepsilonRI-mediated signaling and can recruit the Src homology 2 domain-containing phosphatases Src homology region 2 domain-containing phosphatases 1 and 2. To investigate the specific involvement of the individual ITIMs in this study, mutational analysis was performed, which revealed that both ITIMs are crucial for SIRL-1 inhibitory function and phosphatase recruitment. When primary cells were stimulated in vitro, SIRL-1(high) monocytes produce less TNF-alpha than SIRL-1(low) monocytes. Thus, SIRL-1 is a novel inhibitory immune receptor belonging to the growing family of ITIM-bearing receptors that is implied in the regulation of phagocytes.
Tessa A M Steevels; Robert Jan Lebbink; Geertje H A Westerlaken; Paul J Coffer; Linde Meyaard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-07
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  184     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-07-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4741-8     Citation Subset:  AIM; IM    
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
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MeSH Terms
Amino Acid Motifs
Amino Acid Sequence
Cell Degranulation / genetics,  immunology
Cell Line, Tumor
Mast Cells / immunology,  metabolism
Mice, Inbred BALB C
Molecular Sequence Data
Monocytes / immunology,  metabolism
Neutrophils / immunology,  metabolism
Phagocytes / immunology*,  metabolism*
Receptors, IgE / antagonists & inhibitors
Receptors, Immunologic / biosynthesis*,  chemistry,  genetics*,  physiology
Sequence Homology, Amino Acid
Signal Transduction / immunology*
Reg. No./Substance:
0/Receptors, IgE; 0/Receptors, Immunologic; 0/SIRL1 protein, human; 0/leukocyte-associated immunoglobulin-like receptor 1

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