title: C1q-mediated repression of human monocytes is regulated by leukocyte-associated Ig-like receptor 1 (LAIR-1).
abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal function of both the innate and the adaptive immune system, leading to a loss of tolerance to self-antigens. Monocytes are a key component of the innate immune system and are efficient producers of multiple cytokines. In SLE, inappropriate activation of monocytes is thought to contribute to the loss of self-tolerance. In this study, we demonstrate that type 1 interferon (IFN) production by CpG-challenged monocytes can be suppressed by C1q through activating leukocyte-associated Ig-like receptor-1 (LAIR-1), which contains immunoreceptor tyrosine-based inhibition motifs (ITIMs). The phosphorylation of LAIR-1 and the interaction of LAIR-1 with SH2 domain-containing protein tyrosine phosphatase-1 (SHP-1) were enhanced after LAIR-1 engagement by C1q. Moreover, engagement of LAIR-1 by C1q inhibited nuclear translocation of interferon regulatory factor (IRF)-3 and IRF5 in CpG-stimulated monocytes. These data suggest a model in which LAIR-1 engagement by C1q helps maintain monocyte tolerance, specifically with respect to Toll-like receptor-9-mediated monocyte activation.
authors.affiliation: Center for Autoimmune and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Myoungsun
authors.initials: M
authors.lastname: Son
authors.affiliation: Center for Autoimmune and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
mesh_terms: D002478:Cells, Cultured; D015922:Complement C1q / Q000378:metabolism*; D018899:CpG Islands; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6; D009000:Monocytes / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C108073:leukocyte-associated immunoglobulin-like receptor 1; D015922:Complement C1q; D007371:Interferon-gamma; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6