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An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation.


ABSTRACT: An adaptive immune response triggered by obesity is characterized by the activation of adipose tissue CD4(+) T cells by unclear mechanisms. We have examined whether interactions between adipose tissue macrophages (ATMs) and CD4(+) T cells contribute to adipose tissue metainflammation. Intravital microscopy identifies dynamic antigen-dependent interactions between ATMs and T cells in visceral fat. Mice deficient in major histocompatibility complex class II (MHC II) showed protection from diet-induced obesity. Deletion of MHC II expression in macrophages led to an adipose tissue-specific decrease in the effector/memory CD4(+) T cells, attenuation of CD11c(+) ATM accumulation, and improvement in glucose intolerance by increasing adipose tissue insulin sensitivity. Ablation experiments demonstrated that the maintenance of proliferating conventional T cells is dependent on signals from CD11c(+) ATMs in obese mice. These studies demonstrate the importance of MHCII-restricted signals from ATMs that regulate adipose tissue T cell maturation and metainflammation.

SUBMITTER: Cho KW 

PROVIDER: S-EPMC4252867 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation.

Cho Kae Won KW   Morris David L DL   DelProposto Jennifer L JL   Geletka Lynn L   Zamarron Brian B   Martinez-Santibanez Gabriel G   Meyer Kevin A KA   Singer Kanakadurga K   O'Rourke Robert W RW   Lumeng Carey N CN  

Cell reports 20141009 2


An adaptive immune response triggered by obesity is characterized by the activation of adipose tissue CD4(+) T cells by unclear mechanisms. We have examined whether interactions between adipose tissue macrophages (ATMs) and CD4(+) T cells contribute to adipose tissue metainflammation. Intravital microscopy identifies dynamic antigen-dependent interactions between ATMs and T cells in visceral fat. Mice deficient in major histocompatibility complex class II (MHC II) showed protection from diet-ind  ...[more]

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