title: Siglec-G deficiency leads to more severe collagen-induced arthritis and earlier onset of lupus-like symptoms in MRL/lpr mice.
abstract: Siglec-G is a member of the sialic acid-binding Ig-like lectin (Siglec) family expressed on all B cells. Siglec-G-deficient mice show a large expansion of the B1 cell compartment, demonstrating the crucial role of Siglec-G as an inhibitory receptor on this cellular subset. Although Siglec-G-deficient mice did not develop spontaneous autoimmunity, mice double-deficient for Siglec-G and the related Siglec protein CD22 did show autoimmunity at an older age. In this study, we addressed the question of whether loss of Siglec G on its own affects disease severity in animal models of rheumatoid arthritis and systemic lupus erythematosus. Siglec-G-deficient mice showed moderately increased clinical severity and higher inflammation of the knee joints following collagen-induced arthritis, when compared with control mice. The Siglec-G-deficient mouse was also backcrossed to the autoimmune prone MLR/lpr background. Although both Siglec-G-deficient and control MRL/lpr mice developed a lupus-like disease, Siglec-G-deficient MRL/lpr mice showed an earlier occurrence of autoantibodies; a higher lymphoproliferation of B and T cells; and an earlier onset of disease, as shown by proteinuria and glomerular damage in the kidney. Moreover, Siglec-G-deficient female mice showed a significantly reduced survival compared with female control MRL/lpr mice. Thus, the loss of the inhibitory receptor Siglec-G led to a moderate exacerbation of disease severity and early onset in both collagen-induced arthritis and spontaneous lupus nephritis in MRL/lpr mice.
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91058 Erlangen, Germany;
authors.forename: Susanne
authors.initials: S
authors.lastname: Bökers
authors.forename: Anne
authors.initials: A
authors.lastname: Urbat
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.forename: Marion
authors.initials: M
authors.lastname: Espéli
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D037102:Lectins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D012737:Sex Factors; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000974:Antibodies, Antinuclear; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse