Journal
CLINICAL IMMUNOLOGY
Volume 150, Issue 1, Pages 31-42Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2013.11.007
Keywords
Inhibitory immune receptor; Autoimmune disease; Mouse models; GWAS; Downstream effectors
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Funding
- Dutch Arthritis Foundation [06-1-403]
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Inhibitory receptors are thought to be important in balancing immune responses. The general assumption is that lack of inhibition predisposes for autoimmune diseases. As reviewed here, various experimental and clinical data support this assumption. However, in humans genetic evidence implicates only a limited number of inhibitory receptors. GWAS have established common variation in a few inhibitory receptor genes, such as FC gamma RIIB, PD-1 and CTLA-4 as risk factors. The question arises whether inhibitory receptor function is a major determinant of autoimmune disease. In this respect, the finding that genetic variation in CSK and PTPN22 is strongly associated with multiple autoimmune diseases is of interest. We propose a model in which the molecules encoded by these genes are downstream of inhibitory receptors. We conclude that common genetic variation of inhibitory receptors, with few exceptions, is not a determining factor for autoimmunity in humans. However, common downstream signaling pathways are. (C) 2013 Elsevier Inc. All rights reserved.
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