A New “Immunological” Role for Adipocytes in Obesity Zuzana Hruskova, Subhra K. Biswas  Cell Metabolism  Volume 17, Issue 3, Pages 315-317 (March 2013) DOI: 10.1016/j.cmet.2013.02.015 Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 1 Adipocytes Play an Active Immunological Role in Orchestrating the Immune-Inflammatory Network in Adipose Tissue during Obesity The figure represents some possible interactions between adipocytes, ATMs, ART subsets, and other immune cells which orchestrate chronic low-grade inflammation in the adipose tissue during obesity. During the early phase of obesity (right panel), adipocytes crosstalk with T cells by releasing leptin, which upregulates Th1 polarization and IFNγ production. IFNγ induces upregulation of CIITA and MHCII on adipocytes which instigate MHCII-mediated antigen presentation and an inflammatory Th1 response. Other immune subsets, like CD8+T cells, Th17 cells, and B cells (through antigen presentation to ARTs and pathogenic antibodies), may contribute to this inflammation. In the later phase of obesity, ATMs are recruited in response to chemokines (e.g., CCL2), and the inflammatory microenvironment, potentially via IFNγ and IL-17, polarizes them to an M1 phenotype. By releasing inflammatory cytokines such as TNF and IL-1β, as well as antigen presentation to T cells, M1 ATMs further amplify the adipose tissue inflammation, leading to pathogenesis. In contrast, the events during lean conditions are less understood (left panel). Under lean conditions, Th2 and T-regulatory (Treg) cells dominate the scene. These cells, through the release of IL-4, IL-13, and IL-10, keep ATMs in an M2 phenotype. M2 ATMs, possibly through the release of anti-inflammatory cytokines, IL-10, and scavenging functions, maintain homeostasis in the adipose tissue. Eosinophil (Eos)-derived IL-4 has been reported to drive M2 polarization of ATM. B cell-derived IL-10 is also suggested to contribute to this milieu. However, little is known about the immunological role and antigen-presentation capacity of adipocytes themselves during lean phase, although skewing to Treg or Th2 requires such an interaction, which may come from ATMs as well. [?] indicates possible interactions (or molecules) which are not known or are currently poorly characterized. Arrows indicate interactions and interacting cytokines involved therein. Possible interactions involving other cell types (e.g., NK cells, neutrophils) have not been represented in this simplified figure. Cell Metabolism 2013 17, 315-317DOI: (10.1016/j.cmet.2013.02.015) Copyright © 2013 Elsevier Inc. Terms and Conditions