Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters (original) (raw)

• Shoelson, S.E., Lee, J. & Goldfine, A.B. Inflammation and insulin resistance. J. Clin. Invest. 116, 1793–1801 (2006).
  Article CAS Google Scholar
• Hotamisligil, G.S., Shargill, N.S. & Spiegelman, B.M. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 259, 87–91 (1993).
  Article CAS Google Scholar
• Cai, D. et al. Local and systemic insulin resistance resulting from hepatic activation of IKKβand NF-κB. Nat. Med. 11, 183–190 (2005).
  Article CAS Google Scholar
• Bosello, O. & Zamboni, M. Visceral obesity and metabolic syndrome. Obes. Rev. 1, 47–56 (2000).
  Article CAS Google Scholar
• Fantuzzi, G. Adipose tissue, adipokines and inflammation. J. Allergy Clin. Immunol. 115, 911–919 (2005).
  Article CAS Google Scholar
• Weisberg, S.P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).
  Article CAS Google Scholar
• Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).
  Article CAS Google Scholar
• Lumeng, C.N., Bodzin, J.L. & Saltiel, A.R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175–184 (2007).
  Article CAS Google Scholar
• Lumeng, C.N., Deyoung, S.M., Bodzin, J.L. & Saltiel, A.R. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56, 16–23 (2007).
  Article CAS Google Scholar
• Odegaard, J.I. et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447, 1116–1120 (2007).
  Article CAS Google Scholar
• Suganami, T., Nishida, J. & Ogawa, Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor α. Arterioscler. Thromb. Vasc. Biol. 25, 2062–2068 (2005).
  Article CAS Google Scholar
• Caspar-Bauguil, S. et al. Adipose tissues as an ancestral immune organ: site-specific change in obesity. FEBS Lett. 579, 3487–3492 (2005).
  Article CAS Google Scholar
• Zheng, Y. & Rudensky, A.Y. Foxp3 in control of the regulatory T cell lineage. Nat. Immunol. 8, 457–462 (2007).
  Article CAS Google Scholar
• Sakaguchi, S., Yamaguchi, T., Nomura, T. & Ono, M. Regulatory T cells and immune tolerance. Cell 133, 775–787 (2008).
  Article CAS Google Scholar
• Maloy, K.J. et al. CD4+CD25+ TR cells suppress innate immune pathology through cytokine-dependent mechanisms. J. Exp. Med. 197, 111–119 (2003).
  Article CAS Google Scholar
• Murphy, T.J., Choileain, N.N., Zang, Y., Mannick, J.A. & Lederer, J.A. CD4+CD25+ regulatory T cells control innate immune reactivity after injury. J. Immunol. 174, 2957–2963 (2005).
  Article CAS Google Scholar
• Nguyen, L.T., Jacobs, J., Mathis, D. & Benoist, C. Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis. Arthritis Rheum. 56, 509–520 (2007).
  Article CAS Google Scholar
• Wu, H. et al. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 115, 1029–1038 (2007).
  Article CAS Google Scholar
• Tran, T.T., Yamamoto, Y., Gesta, S. & Kahn, C.R. Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab. 7, 410–420 (2008).
  Article CAS Google Scholar
• Cinti, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46, 2347–2355 (2005).
  Article CAS Google Scholar
• Fontenot, J.D. et al. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 22, 329–341 (2005).
  Article CAS Google Scholar
• Huehn, J. et al. Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J. Exp. Med. 199, 303–313 (2004).
  Article CAS Google Scholar
• Herman, A.E., Freeman, G.J., Mathis, D. & Benoist, C. CD4+CD25+ T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion. J. Exp. Med. 199, 1479–1489 (2004).
  Article CAS Google Scholar
• Hill, J. et al. Foxp3-transcription-factor–dependent and –independent regulation of the regulatory T cell transcriptional signature. Immunity 27, 786–800 (2007).
  Article CAS Google Scholar
• Nolan, K.F. et al. IL-10–conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals. J. Immunol. 172, 2201–2209 (2004).
  Article CAS Google Scholar
• Wong, J. et al. Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory CD4+ T cells. J. Immunol. 178, 7032–7041 (2007).
  Article CAS Google Scholar
• Hsieh, C.S., Zheng, Y., Liang, Y., Fontenot, J.D. & Rudensky, A.Y. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7, 401–410 (2006).
  Article CAS Google Scholar
• Pacholczyk, R., Ignatowicz, H., Kraj, P. & Ignatowicz, L. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells. Immunity 25, 249–259 (2006).
  Article CAS Google Scholar
• Kretschmer, K. et al. Inducing and expanding regulatory T cell populations by foreign antigen. Nat. Immunol. 6, 1219–1227 (2005).
  Article CAS Google Scholar
• Correia-Neves, M., Waltzinger, C., Mathis, D. & Benoist, C. The shaping of the T cell repertoire. Immunity 14, 21–32 (2001).
  Article CAS Google Scholar
• Samad, F., Yamamoto, K., Pandey, M. & Loskutoff, D.J. Elevated expression of transforming growth factor-β in adipose tissue from obese mice. Mol. Med. 3, 37–48 (1997).
  Article CAS Google Scholar
• Chen, W. et al. Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med. 198, 1875–1886 (2003).
  Article CAS Google Scholar
• Peng, Y., Laouar, Y., Li, M.O., Green, E.A. & Flavell, R.A. TGF-β regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc. Natl. Acad. Sci. USA 101, 4572–4577 (2004).
  Article CAS Google Scholar
• Marie, J.C., Letterio, J.J., Gavin, M. & Rudensky, A.Y. TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J. Exp. Med. 201, 1061–1067 (2005).
  Article CAS Google Scholar
• Pelleymounter, M.A. et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543 (1995).
  Article CAS Google Scholar
• Klebig, M.L., Wilkinson, J.E., Geisler, J.G. & Woychik, R.P. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes and yellow fur. Proc. Natl. Acad. Sci. USA 92, 4728–4732 (1995).
  Article CAS Google Scholar
• De Rosa, V. et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity 26, 241–255 (2007).
  Article CAS Google Scholar
• Kim, J.M., Rasmussen, J.P. & Rudensky, A.Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8, 191–197 (2007).
  Article CAS Google Scholar
• Bennett, C.L. & Clausen, B.E. DC ablation in mice: promises, pitfalls and challenges. Trends Immunol. 28, 525–531 (2007).
  Article CAS Google Scholar
• Thorburn, J., Frankel, A.E. & Thorburn, A. Apoptosis by leukemia cell–targeted diphtheria toxin occurs via receptor-independent activation of Fas-associated death domain protein. Clin. Cancer Res. 9, 861–865 (2003).
  CAS PubMed Google Scholar
• Miyake, Y. et al. Protective role of macrophages in noninflammatory lung injury caused by selective ablation of alveolar epithelial type II cells. J. Immunol. 178, 5001–5009 (2007).
  Article CAS Google Scholar
• Bennett, C.L. et al. Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J. Cell Biol. 169, 569–576 (2005).
  Article CAS Google Scholar
• Duffield, J.S. et al. Conditional ablation of macrophages halts progression of crescentic glomerulonephritis. Am. J. Pathol. 167, 1207–1219 (2005).
  Article CAS Google Scholar
• Duffield, J.S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115, 56–65 (2005).
  Article CAS Google Scholar
• Walzer, T. et al. Identification, activation and selective in vivo ablation of mouse NK cells via NKp46. Proc. Natl. Acad. Sci. USA 104, 3384–3389 (2007).
  Article CAS Google Scholar
• Yuan, M. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293, 1673–1677 (2001).
  Article CAS Google Scholar
• Boyman, O., Kovar, M., Rubinstein, M.P., Surh, C.D. & Sprent, J. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 311, 1924–1927 (2006).
  Article CAS Google Scholar
• Tang, Q. et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 28, 687–697 (2008).
  Article CAS Google Scholar
• Wolf, A.M., Wolf, D., Rumpold, H., Enrich, B. & Tilg, H. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem. Biophys. Res. Commun. 323, 630–635 (2004).
  Article CAS Google Scholar
• Kumada, M. et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 109, 2046–2049 (2004).
  Article CAS Google Scholar
• Kim, H.J. et al. Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53, 1060–1067 (2004).
  Article CAS Google Scholar
• Blüher, M. et al. Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. Exp. Clin. Endocrinol. Diabetes 113, 534–537 (2005).
  Article Google Scholar
• Scarpelli, D. et al. Variants of the interleukin-10 promoter gene are associated with obesity and insulin resistance but not type 2 diabetes in Caucasian Italian subjects. Diabetes 55, 1529–1533 (2006).
  Article CAS Google Scholar
• Doganci, A. et al. The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J. Clin. Invest. 115, 313–325 (2005).
  Article CAS Google Scholar
• Wan, S., Xia, C. & Morel, L. IL-6 produced by dendritic cells from lupus-prone mice inhibits CD4+CD25+ T cell regulatory functions. J. Immunol. 178, 271–279 (2007).
  Article CAS Google Scholar
• Hosogai, N. et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56, 901–911 (2007).
  Article CAS Google Scholar
• Furukawa, S. et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114, 1752–1761 (2004).
  Article CAS Google Scholar
• Reich, M. et al. GenePattern 2.0. Nat. Genet. 38, 500–501 (2006).
  Article CAS Google Scholar