Invariant natural killer T cells in adipose tissue: novel regulators of immune-mediated metabolic disease
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Cellular and Molecular Life Sciences
Review
Invariant natural killer T cells in adipose tissue: novel regulators of immune‑mediated metabolic disease M. Rakhshandehroo · E. Kalkhoven · M. Boes
Received: 27 March 2013 / Revised: 19 June 2013 / Accepted: 20 June 2013 / Published online: 9 July 2013 © Springer Basel 2013
Abstract Adipose tissue (AT) represents a microenvironment where intersection takes place between immune processes and metabolic pathways. A variety of immune cells have been characterized in AT over the past decades, with the most recent addition of invariant natural killer T (iNKT) cells. As members of the T cell family, iNKT cells represent a subset that exhibits both innate and adaptive characteristics and directs ensuing immune responses. In disease conditions, iNKT cells have established roles that include disorders in the autoimmune spectrum in malignancies and infectious diseases. Recent work supports a role for iNKT cells in the maintenance of AT homeostasis through both immune and metabolic pathways. The deficiency of iNKT cells can result in AT metabolic disruptions and insulin resistance. In this review, we summarize recent work on iNKT cells in immune regulation, with an emphasis on ATresident iNKT cells, and identify the potential mechanisms by which adipocytes can mediate iNKT cell activity. Keywords Invariant natural killer T cells · Insulin resistance · Obesity · Type II diabetes · Adipose tissue · Immune regulation
E. Kalkhoven and M. Boes contributed equally to this work. M. Rakhshandehroo · E. Kalkhoven (*) Section Metabolic Diseases, Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands e-mail: [email protected] M. Boes (*) Department of Pediatric Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands e-mail: [email protected]
Introduction Immunometabolism Obesity is associated with an expansion of adipose tissue (AT), a major site of energy storage in the body. AT used to be viewed as a long-term energy-storage organ but research performed in the last decades has clarified that AT, most notably visceral AT (VAT) (i.e., omental or epididymal fat), is a site where the immune system and metabolic cascades are integrated [1–7]. Experiments performed in mouse models and using human VAT demonstrated the interplay between metabolic and immunological health and derailment of both upon development of metabolic disease. In healthy VAT, immune cells are distributed sparsely amongst adipocytes, however, during obesity, local inflammation prompts the infiltration of both pro- and anti-inflammatory immune cells in AT while adipocytes themselves become hypertrophic (Fig. 1). Infiltration of immune cells is a key event that links inflammation with AT-intrinsic and systemic metabolic changes [8–10]. Considering this phenomenon in the context of obesity, adipocyte hypertrophy is caused by excess lipid storage, and leads to the activation of distinct metabolic and stress sig
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