title: Do inhibitory immune receptors play a role in the etiology of autoimmune disease?
abstract: 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 FCγRIIB, 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.
authors: Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, The Netherlands.
authors: Marloes J M
authors: MJ
authors: Olde Nordkamp
authors: Section Complex Genetics, Department of Medical Genetics, University Medical Centre Utrecht, The Netherlands.
authors: Bobby P
authors: BP
authors: Koeleman
authors: Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, The Netherlands. Electronic address: l.meyaard@umcutrecht.nl.
authors: Linde
authors: L
authors: Meyaard
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D006801:Humans; D011971:Receptors, Immunologic / Q000276:immunology*
chemical_list: D011971:Receptors, Immunologic
keywords: Autoimmune disease; Downstream effectors; GWAS; Inhibitory immune receptor; Mouse models