title: Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity.
abstract: Obesity-induced inflammation in visceral adipose tissue (VAT) is a major contributor to insulin resistance and type 2 diabetes. Whereas innate immune cells, notably macrophages, contribute to visceral adipose tissue (VAT) inflammation and insulin resistance, the role of adaptive immunity is less well defined. To address this critical gap, we used a model in which endogenous activation of T cells was suppressed in obese mice by blocking MyD88-mediated maturation of CD11c+ antigen-presenting cells. VAT CD11c+ cells from Cd11cCre+Myd88fl/fl vs. control Myd88fl/fl mice were defective in activating T cells in vitro, and VAT T and B cell activation was markedly reduced in Cd11cCre+Myd88fl/fl obese mice. However, neither macrophage-mediated VAT inflammation nor systemic inflammation were altered in Cd11cCre+Myd88fl/fl mice, thereby enabling a focused analysis on adaptive immunity. Unexpectedly, fasting blood glucose, plasma insulin, and the glucose response to glucose and insulin were completely unaltered in Cd11cCre+Myd88fl/fl vs. control obese mice. Thus, CD11c+ cells activate VAT T and B cells in obese mice, but suppression of this process does not have a discernible effect on macrophage-mediated VAT inflammation or systemic glucose homeostasis.
authors: Department of Medicine, Columbia University, New York, NY, 10032, United States of America.
authors: Manikandan
authors: M
authors: Subramanian
authors: Department of Medicine, Columbia University, New York, NY, 10032, United States of America.
authors: Lale
authors: L
authors: Ozcan
authors: Department of Medicine, Columbia University, New York, NY, 10032, United States of America.
authors: Devram Sampat
authors: DS
authors: Ghorpade
authors: Department of Medicine, Columbia University, New York, NY, 10032, United States of America.
authors: Anthony W
authors: AW
authors: Ferrante
authors: Department of Medicine, Columbia University, New York, NY, 10032, United States of America; Department of Pathology & Cell Biology, Columbia University, New York, NY, 10032, United States of America; Department of Physiology & Cellular Biophysics, Columbia University, New York, NY, 10032, United States of America.
authors: Ira
authors: I
authors: Tabas
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000276:immunology* / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88