Molecules and Cells

, Volume 33, Issue 3, pp 217–222

The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases

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Abstract

Members of the nuclear receptor superfamily function as transcription factors involved in innate and adaptive immunity as well as lipid metabolism. These highly conserved proteins participate in ligand-dependent or -independent regulatory mechanisms that affect gene expression. Peroxisome proliferator-activated receptors (PPARs), which include PPARα, PPARβ/δ, and PPARΓ, are a group of nuclear receptor proteins that play diverse roles in cellular differentiation, development, and metabolism. Each PPAR subfamily is activated by different endogenous and synthetic ligands. Recent studies using specific ligand treatments and cell type-specific PPAR knockout mice have revealed important roles for these proteins in T-cell-related autoimmune diseases. Moreover, PPARs have been shown to regulate T-cell survival, activation, and CD4+ T helper cell differentiation into the Th1, Th2, Th17, and Treg lineages. Here, we review the studies that provide insight into the important regulatory roles of PPARs in T-cell activation, survival, proliferation, differentiation, and autoimmune disease.

Keywords

autoimmune disease nuclear receptor PPAR T cell 

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References

  1. Agostini, M., Schoenmakers, E., Mitchell, C., Szatmari, I., Savage, D., Smith, A., Rajanayagam, O., Semple, R., Luan, J., Bath, L., et al. (2006). Non-DNA binding, dominant-negative, human PPARgamma mutations cause lipodystrophic insulin resistance. Cell Metab. 4, 303–311.PubMedCrossRefGoogle Scholar
  2. Akiyama, T.E., Baumann, C.T., Sakai, S., Hager, G.L., and Gonzalez, F.J. (2002). Selective intranuclear redistribution of PPAR isoforms by RXR alpha. Mol. Endocrinol. 16, 707–721.PubMedCrossRefGoogle Scholar
  3. Azuma, Y.T., Nishiyama, K., Matsuo, Y., Kuwamura, M., Morioka, A., Nakajima, H., and Takeuchi, T. (2010). PPARalpha contributes to colonic protection in mice with DSS-induced colitis. Int. Immunopharmacol. 10, 1261–1267.PubMedCrossRefGoogle Scholar
  4. Baratelli, F., Lin, Y., Zhu, L., Yang, S.C., Heuze-Vourc’h, N., Zeng, G., Reckamp, K., Dohadwala, M., Sharma, S., and Dubinett, S.M. (2005). Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J. Immunol. 175, 1483–1490.PubMedGoogle Scholar
  5. Barish, G.D., Atkins, A.R., Downes, M., Olson, P., Chong, L.W., Nelson, M., Zou, Y., Hwang, H., Kang, H., Curtiss, L., et al. (2008). PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis. Proc. Natl. Acad. Sci. USA 105, 4271–4276.PubMedCrossRefGoogle Scholar
  6. Barroso, I., Gurnell, M., Crowley, V.E., Agostini, M., Schwabe, J.W., Soos, M.A., Maslen, G.L., Williams, T.D., Lewis, H., Schafer, A.J., et al. (1999). Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402, 880–883.PubMedGoogle Scholar
  7. Berger, J., Leibowitz, M.D., Doebber, T.W., Elbrecht, A., Zhang, B., Zhou, G., Biswas, C., Cullinan, C.A., Hayes, N.S., Li, Y., et al. (1999). Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J. Biol. Chem. 274, 6718–6725.PubMedCrossRefGoogle Scholar
  8. Chan, M.M., Evans, K.W., Moore, A.R., and Fong, D. (2010). Peroxisome proliferator-activated receptor (PPAR): balance for survival in parasitic infections. J. Biomed. Biotechnol. 2010, 828951.PubMedCrossRefGoogle Scholar
  9. Chandra, V., Huang, P., Hamuro, Y., Raghuram, S., Wang, Y., Burris, T.P., and Rastinejad, F. (2008). Structure of the intact PPAR-gamma-RXR-nuclear receptor complex on DNA. Nature 456, 350–356.PubMedCrossRefGoogle Scholar
  10. Chawla, A., Repa, J.J., Evans, R.M., and Mangelsdorf, D.J. (2001) Nuclear receptors and lipid physiology: opening the X-files. Science 294, 1866–1870.PubMedCrossRefGoogle Scholar
  11. Choi, J.M., Ahn, M.H., Chae, W.J., Jung, Y.G., Park, J.C., Song, H.M., Kim, Y.E., Shin, J.A., Park, C.S., Park, J.W., et al. (2006). Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. Nat. Med. 12, 574–579.PubMedCrossRefGoogle Scholar
  12. Choi, J.M., Shin, J.H., Sohn, M.H., Harding, M.J., Park, J.H., Tobiasova, Z., Kim, D.Y., Maher, S.E., Chae, W.J., Park, S.H., et al. (2010). Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proc. Natl. Acad. Sci. USA 107, 18575–18580.PubMedCrossRefGoogle Scholar
  13. Clark, R.B., Bishop-Bailey, D., Estrada-Hernandez, T., Hla, T., Puddington, L., and Padula, S.J. (2000). The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J. Immunol. 164, 1364–1371.PubMedGoogle Scholar
  14. Daynes, R.A., and Jones, D.C. (2002). Emerging roles of PPARs in inflammation and immunity. Nat. Rev. Immunol. 2, 748–759.PubMedCrossRefGoogle Scholar
  15. Delerive, P., De Bosscher, K., Besnard, S., Vanden Berghe, W., Peters, J.M., Gonzalez, F.J., Fruchart, J.C., Tedgui, A., Haegeman, G., and Staels, B. (1999). Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J. Biol. Chem. 274, 32048–32054.PubMedCrossRefGoogle Scholar
  16. Desreumaux, P., Dubuquoy, L., Nutten, S., Peuchmaur, M., Englaro, W., Schoonjans, K., Derijard, B., Desvergne, B., Wahli, W., Chambon, P., et al. (2001). Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies. J. Exp. Med. 193, 827–838.PubMedCrossRefGoogle Scholar
  17. Dunn, S.E., Ousman, S.S., Sobel, R.A., Zuniga, L., Baranzini, S.E., Youssef, S., Crowell, A., Loh, J., Oksenberg, J., and Steinman, L. (2007). Peroxisome proliferator-activated receptor (PPAR) alpha expression in T cells mediates gender differences in development of T cell-mediated autoimmunity. J. Exp. Med. 204, 321–330.PubMedCrossRefGoogle Scholar
  18. Dunn, S.E., Bhat, R., Straus, D.S., Sobel, R.A., Axtell, R., Johnson, A., Nguyen, K., Mukundan, L., Moshkova, M., Dugas, J.C., et al. (2010) Peroxisome proliferator-activated receptor delta limits the expansion of pathogenic Th cells during central nervous system autoimmunity. J. Exp. Med. 207, 1599–1608.PubMedCrossRefGoogle Scholar
  19. Fajas, L., Auboeuf, D., Raspe, E., Schoonjans, K., Lefebvre, A.M., Saladin, R., Najib, J., Laville, M., Fruchart, J.C., Deeb, S., et al. (1997). The organization, promoter analysis, and expression of the human PPARgamma gene. J. Biol. Chem. 272, 18779–18789.PubMedCrossRefGoogle Scholar
  20. Forman, B.M., Tontonoz, P., Chen, J., Brun, R.P., Spiegelman, B. M., and Evans, R.M. (1995). 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83, 803–812.PubMedCrossRefGoogle Scholar
  21. Forman, B.M., Chen, J., and Evans, R.M. (1997). Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc. Natl. Acad. Sci. USA 94, 4312–4317.PubMedCrossRefGoogle Scholar
  22. Gervois, P., Fruchart, J.C., and Staels, B. (2007). Drug Insight:mechanisms of action and therapeutic applications for agonists of peroxisome proliferator-activated receptors. Nat. Clin. Pract. Endocrinol. Metab. 3, 145–156.PubMedCrossRefGoogle Scholar
  23. Glass, C.K., and Ogawa, S. (2006). Combinatorial roles of nuclear receptors in inflammation and immunity. Nat. Rev. Immunol. 6, 44–55.PubMedCrossRefGoogle Scholar
  24. Glass, C.K., and Saijo, K. (2010). Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat. Rev. Immunol. 10, 365–376.PubMedCrossRefGoogle Scholar
  25. Gocke, A.R., Hussain, R.Z., Yang, Y., Peng, H., Weiner, J., Ben, L.H., Drew, P.D., Stuve, O., Lovett-Racke, A.E., and Racke, M.K. (2009). Transcriptional modulation of the immune response by peroxisome proliferator-activated receptor-{alpha} agonists in autoimmune disease. J. Immunol. 182, 4479–4487.PubMedCrossRefGoogle Scholar
  26. Gosset, P., Charbonnier, A.S., Delerive, P., Fontaine, J., Staels, B., Pestel, J., Tonnel, A.B., and Trottein, F. (2001). Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells. Eur. J. Immunol. 31, 2857–2865.PubMedCrossRefGoogle Scholar
  27. Guan, H.P., Ishizuka, T., Chui, P.C., Lehrke, M., and Lazar, M.A. (2005). Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes. Genes Dev. 19, 453–461.PubMedCrossRefGoogle Scholar
  28. Guri, A.J., Mohapatra, S.K., Horne, W.T., 2nd, Hontecillas, R., and Bassaganya-Riera, J. (2010). The role of T cell PPAR gamma in mice with experimental inflammatory bowel disease. BMC Gastroenterol. 10, 60.PubMedCrossRefGoogle Scholar
  29. Harris, S.G., and Phipps, R.P. (2001). The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis. Eur. J. Immunol. 31, 1098–1105.PubMedCrossRefGoogle Scholar
  30. Hegele, R.A., Cao, H., Frankowski, C., Mathews, S.T., and Leff, T. (2002). PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes 51, 3586–3590.PubMedCrossRefGoogle Scholar
  31. Hontecillas, R., and Bassaganya-Riera, J. (2007). Peroxisome proliferator-activated receptor gamma is required for regulatory CD4+ T cell-mediated protection against colitis. J. Immunol. 178, 2940–2949.PubMedGoogle Scholar
  32. Housley, W.J., Adams, C.O., Vang, A.G., Brocke, S., Nichols, F.C., LaCombe, M., Rajan, T.V., and Clark, R.B. (2011). Peroxisome proliferator-activated receptor gamma is required for CD4+ T cell-mediated lymphopenia-associated autoimmunity. J. Immunol. 187, 4161–4169.PubMedCrossRefGoogle Scholar
  33. Itoh, T., Fairall, L., Amin, K., Inaba, Y., Szanto, A., Balint, B.L., Nagy, L., Yamamoto, K., and Schwabe, J.W. (2008). Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat. Struct. Mol. Biol. 15, 924–931.PubMedCrossRefGoogle Scholar
  34. Jiang, C., Ting, A.T., and Seed, B. (1998). PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82–86.PubMedCrossRefGoogle Scholar
  35. Jo, S.H., Yang, C., Miao, Q., Marzec, M., Wasik, M.A., Lu, P., and Wang, Y.L. (2006). Peroxisome proliferator-activated receptor gamma promotes lymphocyte survival through its actions on cellular metabolic activities. J. Immunol. 177, 3737–3745.PubMedGoogle Scholar
  36. Jones, D.C., Ding, X., and Daynes, R.A. (2002). Nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is expressed in resting murine lymphocytes. The PPARalpha in T and B lymphocytes is both transactivation and transrepression competent. J. Biol. Chem. 277, 6838–6845.PubMedCrossRefGoogle Scholar
  37. Kanakasabai, S., Chearwae, W., Walline, C.C., Iams, W., Adams, S.M., and Bright, J.J. (2010). Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis. Immunology 130, 572–588.PubMedCrossRefGoogle Scholar
  38. Kliewer, S.A., Forman, B.M., Blumberg, B., Ong, E.S., Borgmeyer, U., Mangelsdorf, D.J., Umesono, K., and Evans, R.M. (1994). Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. USA 91, 7355–7359.PubMedCrossRefGoogle Scholar
  39. Kliewer, S.A., Sundseth, S.S., Jones, S.A., Brown, P.J., Wisely, G.B., Koble, C.S., Devchand, P., Wahli, W., Willson, T.M., Lenhard, J.M., et al. (1997). Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc. Natl. Acad. Sci. USA 94, 4318–4323.PubMedCrossRefGoogle Scholar
  40. Klotz, L., Dani, I., Edenhofer, F., Nolden, L., Evert, B., Paul, B., Kolanus, W., Klockgether, T., Knolle, P., and Diehl, L. (2007). Peroxisome proliferator-activated receptor gamma control of dendritic cell function contributes to development of CD4+ T cell anergy. J. Immunol. 178, 2122–2131.PubMedGoogle Scholar
  41. Klotz, L., Burgdorf, S., Dani, I., Saijo, K., Flossdorf, J., Hucke, S., Alferink, J., Nowak, N., Beyer, M., Mayer, G., et al. (2009). The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J. Exp. Med. 206, 2079–2089.PubMedCrossRefGoogle Scholar
  42. Lee, J.W., Bajwa, P.J., Carson, M.J., Jeske, D.R., Cong, Y., Elson, C.O., Lytle, C., and Straus, D.S. (2007). Fenofibrate represses interleukin-17 and interferon-gamma expression and improves colitis in interleukin-10-deficient mice. Gastroenterology 133, 108–123.PubMedCrossRefGoogle Scholar
  43. Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., Wilkison, W.O., Willson, T.M., and Kliewer, S.A. (1995). An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferatoractivated receptor gamma (PPAR gamma). J. Biol. Chem. 270, 12953–12956.PubMedCrossRefGoogle Scholar
  44. Mangelsdorf, D.J., Thummel, C., Beato, M., Herrlich, P., Schutz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995). The nuclear receptor superfamily: the second decade. Cell 83, 835–839.PubMedCrossRefGoogle Scholar
  45. McKenna, N.J., and O’Malley, B.W. (2002). Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 108, 465–474.PubMedCrossRefGoogle Scholar
  46. Moras, D., and Gronemeyer, H. (1998). The nuclear receptor ligand-binding domain: structure and function. Curr. Opin. Cell Biol. 10, 384–391.PubMedCrossRefGoogle Scholar
  47. Ogawa, S., Lozach, J., Benner, C., Pascual, G., Tangirala, R.K., Westin, S., Hoffmann, A., Subramaniam, S., David, M., Rosenfeld, M.G., et al. (2005). Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122, 707–721.PubMedCrossRefGoogle Scholar
  48. Oliver, W.R., Jr., Shenk, J.L., Snaith, M.R., Russell, C.S., Plunket, K.D., Bodkin, N.L., Lewis, M.C., Winegar, D.A., Sznaidman, M. L., Lambert, M.H., et al. (2001). A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc. Natl. Acad. Sci. USA 98, 5306–5311.PubMedCrossRefGoogle Scholar
  49. Pascual, G., Fong, A.L., Ogawa, S., Gamliel, A., Li, A.C., Perissi, V., Rose, D.W., Willson, T.M., Rosenfeld, M.G., and Glass, C.K. (2005). A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437, 759–763.PubMedCrossRefGoogle Scholar
  50. Peraza, M.A., Burdick, A.D., Marin, H.E., Gonzalez, F.J., and Peters, J.M. (2006). The toxicology of ligands for peroxisome pro-liferator-activated receptors (PPAR). Toxicol. Sci. 90, 269–295.PubMedCrossRefGoogle Scholar
  51. Polak, P.E., Kalinin, S., Dello Russo, C., Gavrilyuk, V., Sharp, A., Peters, J.M., Richardson, J., Willson, T.M., Weinberg, G., and Feinstein, D.L. (2005). Protective effects of a peroxisome proliferator-activated receptor-beta/delta agonist in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 168, 65–75.PubMedCrossRefGoogle Scholar
  52. Renaud, J.P., Rochel, N., Ruff, M., Vivat, V., Chambon, P., Gronemeyer, H., and Moras, D. (1995). Crystal structure of the RARgamma ligand-binding domain bound to all-trans retinoic acid. Nature 378, 681–689.PubMedCrossRefGoogle Scholar
  53. Ricote, M., Li, A.C., Willson, T.M., Kelly, C.J., and Glass, C.K. (1998). The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391, 79–82.PubMedCrossRefGoogle Scholar
  54. Ristow, M., Muller-Wieland, D., Pfeiffer, A., Krone, W., and Kahn, C.R. (1998). Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N. Engl. J. Med. 339, 953–959.PubMedCrossRefGoogle Scholar
  55. Sanderson, L.M., Degenhardt, T., Koppen, A., Kalkhoven, E., Desvergne, B., Muller, M., and Kersten, S. (2009). Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver. Mol. Cell. Biol. 29, 6257–6267.PubMedCrossRefGoogle Scholar
  56. Setoguchi, K., Misaki, Y., Terauchi, Y., Yamauchi, T., Kawahata, K., Kadowaki, T., and Yamamoto, K. (2001). Peroxisome proliferator-activated receptor-gamma haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis. J. Clin. Invest. 108, 1667–1675.PubMedGoogle Scholar
  57. Su, C.G., Wen, X., Bailey, S.T., Jiang, W., Rangwala, S.M., Keilbaugh, S.A., Flanigan, A., Murthy, S., Lazar, M.A., and Wu, G.D. (1999a). A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J. Clin. Invest. 104, 383–389.PubMedCrossRefGoogle Scholar
  58. Su, J.L., Winegar, D.A., Wisely, G.B., Sigel, C.S., and Hull-Ryde, E.A. (1999b). Use of a PPAR gamma-specific monoclonal antibody to demonstrate thiazolidinediones induce PPAR gamma receptor expression in vitro. Hybridoma 18, 273–280.PubMedCrossRefGoogle Scholar
  59. Szanto, A., Balint, B.L., Nagy, Z.S., Barta, E., Dezso, B., Pap, A., Szeles, L., Poliska, S., Oros, M., Evans, R.M., et al. (2010). STAT6 transcription factor is a facilitator of the nuclear receptor PPARgamma-regulated gene expression in macrophages and dendritic cells. Immunity 33, 699–712.PubMedCrossRefGoogle Scholar
  60. Szatmari, I., Pap, A., Ruhl, R., Ma, J.X., Illarionov, P.A., Besra, G.S., Rajnavolgyi, E., Dezso, B., and Nagy, L. (2006). PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J. Exp. Med. 203, 2351–2362.PubMedCrossRefGoogle Scholar
  61. Szatmari, I., Torocsik, D., Agostini, M., Nagy, T., Gurnell, M., Barta, E., Chatterjee, K., and Nagy, L. (2007). PPARgamma regulates the function of human dendritic cells primarily by altering lipid metabolism. Blood 110, 3271–3280.PubMedCrossRefGoogle Scholar
  62. Takata, Y., Liu, J., Yin, F., Collins, A.R., Lyon, C.J., Lee, C.H., Atkins, A.R., Downes, M., Barish, G.D., Evans, R.M., et al. (2008). PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc. Natl. Acad. Sci. USA 105, 4277–4282.PubMedCrossRefGoogle Scholar
  63. Tobiasova, Z., Zhang, L., Yi, T., Qin, L., Manes, T.D., Kulkarni, S., Lorber, M.I., Rodriguez, F.C., Choi, J.M., Tellides, G., et al. (2011). Peroxisome proliferator-activated receptor-gamma agonists prevent in vivo remodeling of human artery induced by alloreactive T cells. Circulation 124, 196–205.PubMedCrossRefGoogle Scholar
  64. Varga, T., Czimmerer, Z., and Nagy, L. (2011). PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim. Biophys. Acta 1812, 1007–1022.PubMedGoogle Scholar
  65. Wang, Y.L., Frauwirth, K.A., Rangwala, S.M., Lazar, M.A., and Thompson, C.B. (2002). Thiazolidinedione activation of peroxisome proliferator-activated receptor gamma can enhance mitochondrial potential and promote cell survival. J. Biol. Chem. 277, 31781–31788.PubMedCrossRefGoogle Scholar
  66. Wohlfert, E.A., Nichols, F.C., Nevius, E., and Clark, R.B. (2007). Peroxisome proliferator-activated receptor gamma (PPAR gamma) and immunoregulation: enhancement of regulatory T cells through PPARgamma-dependent and -independent mechanisms. J. Immunol. 178, 4129–4135.PubMedGoogle Scholar
  67. Yang, X.Y., Wang, L.H., Chen, T., Hodge, D.R., Resau, J.H., Da Silva, L., and Farrar, W.L. (2000). Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PPARgamma co-association with transcription factor NFAT. J. Biol. Chem. 275, 4541–4544.Google Scholar
  68. Yang, Y., Lovett-Racke, A.E., and Racke, M.K. (2010). Regulation of immune responses and autoimmune encephalomyelitis by PPARs. PPAR Res. 2010, 104705.PubMedCrossRefGoogle Scholar
  69. Zieleniak, A., Wojcik, M., and Wozniak, L.A. (2008). Structure and physiological functions of the human peroxisome proliferatoractivated receptor gamma. Arch. Immunol. Ther. Exp. (Warsz) 56, 331–345.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2012

Authors and Affiliations

  1. 1.Department of Life Science, Research Institute for Natural SciencesHanyang UniverstiySeoulKorea
  2. 2.Hanyang Biomedical Research InstituteHanyang UniverstiySeoulKorea
  3. 3.Department of ImmunobiologyYale University School of MedicineNew HavenUSA

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