title: IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells and Restraining Autoantibody Production in Congenic Lupus-Prone Mice.
abstract: The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB) strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations.
authors.affiliation: Department of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Baglaenko
authors.affiliation: Department of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kieran P
authors.initials: KP
authors.lastname: Manion
authors.affiliation: Department of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Nan-Hua
authors.initials: NH
authors.lastname: Chang
authors.affiliation: Department of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Gracey
authors.affiliation: Department of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Loh
authors.affiliation: Department of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Wither
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018956:CD5 Antigens; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; C556062:IL10 protein, mouse; D016753:Interleukin-10