Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity

PloS One
Manikandan SubramanianIra Tabas

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 glucos...Continue Reading

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Jan 29, 2020·The Journal of Clinical Endocrinology and Metabolism·Nels C OlsonJoseph A Delaney
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Mar 7, 2021·International Journal of Molecular Sciences·Yetirajam Rajesh, Devanand Sarkar
Jun 1, 2021·Immunopharmacology and Immunotoxicology·Payam Hashemi, Shaghayegh Pezeshki
Oct 23, 2021·JCI Insight·Jae-Su MoonYun Sok Lee

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Methods Mentioned

BETA
PCR
flow-cytometry
ELISA
transgenic
flow cytometry

Software Mentioned

ImagePro
FlowJo

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