Invariant NKT cell serves as a novel therapeutic target for control of obesity

References

• Lynch L, Nowak M, Varghese B et al. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37(3), 574–587 (2012).
   Google Scholar
• Lynch L, O’Shea D, Winter DC, Geoghegan J, Doherty DG, O’Farrelly C. Invariant NKT cells and CD1d+ cells amass in human omentum and are depleted in patients with cancer and obesity. Eur. J. Immunol. 39(7), 1893–1901 (2009). ▪▪ Demonstration that human omentum contains abundant innate T cells – invariant NKT cells, CD56+CD3+ cells (probably type II NKT cells) and NK cells – and the important relevance to cancer and obesity.
   Google Scholar
• Schipper HS, Rakhshandehroo M, van de Graaf SFJ et al. Natural killer T cells in adipose tissue prevent insulin resistance. J. Clin. Invest. 122, 3343–3354 (2012). ▪▪ Shows that adipocytes express CD1d and interact with NKT cells, suggesting direct interactions.
   Google Scholar
• Ji Y, Sun S, Xu A et al. Activation of natural killer T cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via the IL-4/STAT6 signaling axis in obesity. J. Biol Chem. 287, 13561–13571 (2012).
   Google Scholar
• Satoh M, Andoh Y, Clingan CS et al. Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance. PLoS ONE 7, e30568 (2012).
   Google Scholar
• Wu L, Parekh VV, Gabriel CL et al. Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obsess mice. Proc. Natl Acad. Sci. USA 109(19), e1143–e1152 (2012).
   Google Scholar
• Mantell BS, Stefanovic-Racic M, Yang X et al. Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity. PLoS ONE 6, e19831 (2011).
   Google Scholar
• Kotas ME, Lee H-Y, Gillum MO et al. Impact of CD1d deficiency on metabolism. PLoS ONE 6, e25478 (2011).
   Google Scholar
• Wu L, van Kaer L. Contribution of lipidreactive natural killer T cells to obesity-associated inflammation and insulin resistance. Adipocyte 2(1), 12–16 (2013). ▪▪ Summarizes experimental systems in the current literature on the relationship between NKT cells and insulin resistance.
   Google Scholar
• Minami K, Yanagawa Y, Iwabuchi K et al. Negative feedback regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions. Blood 106, 1685–1693 (2005).
   Google Scholar
• Nakai Y, Iwabuchi K, Fujii S et al. Natural killer T cells accelerate atherogenesis in mice. Blood 104, 2051–2059 (2004).
   Google Scholar
• Tupin E, Nicoletti A, Elhage R et al. CD1d-dependent activation of NKT cells aggravates atherosclerosis. J. Exp. Med. 199, 417–422 (2004).
   Google Scholar
• Major AS, Wilson MT, McCaleb JL et al. Quantitative and qualitative differences in proatherogenic NKT cells in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 24, 2351–2357 (2004).
   Google Scholar
• Aslanian AM, Chapman HA, Charo IF. Transient role for CD1d-restricted natural killer T cells in the formation of athersclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 25, 628–632 (2005).
   Google Scholar
• VanderLaan PA, Reardon CA, Sagiv Y et al. Characterization of the natural killer T-cell response in an adoptive transfer model of atherosclerosis. Am. J. Pathol. 170, 1100–1107 (2007).
   Google Scholar
• Rogers L, Burchat S, Gage J et al. Deficiency of invariant Va14 natural killer T cells decreses atherosclerosis in LDL receptor null mice. Cardiovasc. Res. 78, 167–174 (2008).
   Google Scholar
• To K, Agrotis A, Besra G et al. NKT cell subsets mediate differential proatherogenic effects in ApoE-/- mice. Arterioscler. Thromb. Vasc. Biol. 29, 671–677 (2009).
   Google Scholar
• van Puijvelde GH, van Wanrooij EJ, Hauer AD et al. Effect of natural killer T cell activation on the initiation of atherosclerosis. Thromb. Haemost. 102, 223–230 (2009).
   Google Scholar
• Wakao H, Wakao R, Sakata S et al. In vitro induction of natural killer T cells from embryonic stem cells prepared using somatic cell nuclear transfer. FASEB J. 22, 2223–2231 (2008).
   Google Scholar
• Watarai H, Fujii S, Yamada D et al. Murine induced pluripotent stem cells can be derived from and differentiate into natural killer T cells. J. Clin. Invest. 120, 2610–2618 (2010).
   Google Scholar