An MHC II-Dependent Activation Loop between Adipose Tissue Macrophages and CD4(+) T Cells Controls Obesity-Induced Inflammation

作者：Cho Kae Won; Morris David L; DelProposto Jennifer L; Geletka Lynn; Zamarron Brian; Martinez Santibanez Gabriel; Meyer Kevin A; Singer Kanakadurga; O'Rourke Robert W; Lumeng Carey N^*

来源：Cell Reports, 2014, 9(2): 605-617.

DOI：10.1016/j.celrep.2014.09.004

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.

• 出版日期2014-10-23