PPARγ negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation

PLoS ONE

Volumn 9, Issue 6, 2014, Pages

  Park, Hong Jai ^a,b   Kim, Do Hyun ^a,b   Choi, Jin Young ^c   Kim, Won Ju ^a,b   Kim, Ji Yun ^a,b   Senejani, Alireza G ^c   Hwang, Soo Seok ^d   Kim, Lark Kyun ^c   Tobiasova, Zuzana ^c   Lee, Gap Ryol ^c   Craft, Joseph ^c   Bothwell, Alfred L M ^c   Choi, Je Min ^a,b  

^a Hanyang University   (South Korea)

^b Hanyang Biomedical Research Institute   (South Korea)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d Sogang University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; CD4 ANTIGEN; I KAPPA B ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 21; MITOGEN ACTIVATED PROTEIN KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEIN BCL 6; PROTEIN KINASE B; SIRTUIN 1; TRANSCRIPTION FACTOR FKHR; BCL6 PROTEIN, MOUSE; CYTOKINE; DNA BINDING PROTEIN; FORKHEAD TRANSCRIPTION FACTOR; FOXO1 PROTEIN, MOUSE; I KAPPA B KINASE; SIRT1 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; AUTOIMMUNITY; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; FEMALE; GERMINAL CENTER; HELPER CELL; INFANT; INFLAMMATION; MOUSE; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SHEEP ERYTHROCYTE; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH17 CELL; TH2 CELL; TH9 CELL; ANIMAL; CD4+ T LYMPHOCYTE; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; DNA-BINDING PROTEINS; FORKHEAD TRANSCRIPTION FACTORS; GERMINAL CENTER; I-KAPPA B KINASE; LYMPHOCYTE ACTIVATION; MICE; PPAR GAMMA; SIRTUIN 1; T-LYMPHOCYTES, HELPER-INDUCER;

EID: 84903388824     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0099127     Document Type: Article

References (45)

1. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ (2001) Nuclear receptors and lipid physiology: opening the X-files. Science 294: 1866-1870. (Pubitemid 33101573)
2. Evans RM (1988) The steroid and thyroid hormone receptor superfamily. Science 240: 889-895.
3. Glass CK, Ogawa S (2006) Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6: 44-55. (Pubitemid 43279752)
4. Choi JM, Bothwell AL (2012) The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases. Mol Cells 33: 217-222.
5. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, et al. (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 270: 12953-12956.
6. Hsueh WA, Law RE (2001) PPARgamma and atherosclerosis: effects on cell growth and movement. Arterioscler Thromb Vasc Biol 21: 1891-1895. (Pubitemid 34219737)
7. Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, 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. (Pubitemid 32524532)
8. Gervois P, Fruchart JC, 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. (Pubitemid 46146967)
9. Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, et al. (2000) The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J Immunol 164: 1364-1371. (Pubitemid 30067250)
10. Wohlfert EA, Nichols FC, Nevius E, Clark RB (2007) Peroxisome proliferator-activated receptor gamma (PPARgamma) and immunoregulation: enhancement of regulatory T cells through PPARgamma-dependent and -independent mechanisms. J Immunol 178: 4129-4135. (Pubitemid 46492362)
11. Klotz L, Burgdorf S, Dani I, Saijo K, Flossdorf J, 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.
12. Tobiasova Z, Zhang L, Yi T, Qin L, Manes TD, 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.
13. Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, et al. (2012) PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486: 549-553.
14. King C, Tangye SG, Mackay CR (2008) T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol 26: 741-766. (Pubitemid 351600391)
15. Craft JE (2012) Follicular helper T cells in immunity and systemic autoimmunity. Nat Rev Rheumatol 8: 337-347.
16. Sweet RA, Lee SK, Vinuesa CG (2012) Developing connections amongst key cytokines and dysregulated germinal centers in autoimmunity. Curr Opin Immunol 24: 658-664.
17. Crotty S (2011) Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29: 621-663.
18. Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, et al. (2000) Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192: 1545-1552.
19. Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, et al. (2000) CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192: 1553-1562.
20. Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, et al. (2009) Bcl6 mediates the development of T follicular helper cells. Science 325: 1001-1005.
21. Choi YS, Kageyama R, Eto D, Escobar TC, Johnston RJ, et al. (2011) ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 34: 932-946.
22. Simpson N, Gatenby PA, Wilson A, Malik S, Fulcher DA, et al. (2010) Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum 62: 234-244.
23. Park HJ, Kim DH, Lim SH, Kim WJ, Youn J, et al. (2014) Insights into the Role of Follicular Helper T Cells in Autoimmunity. Immune network 14: 21-29.
24. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391: 79-82. (Pubitemid 28079218)
25. Kerdiles YM, Stone EL, Beisner DR, McGargill MA, Ch'en IL, et al. (2010) Foxo transcription factors control regulatory T cell development and function. Immunity 33: 890-904.
26. Zhang J, Lee SM, Shannon S, Gao B, Chen W, et al. (2009) The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice. J Clin Invest 119: 3048-3058.
27. Xue HH, Kovanen PE, Pise-Masison CA, Berg M, Radovich MF, et al. (2002) IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes. Proc Natl Acad Sci U S A 99: 13759-13764. (Pubitemid 35215454)
28. Liu YJ, Malisan F, de Bouteiller O, Guret C, Lebecque S, et al. (1996) Within germinal centers, isotype switching of immunoglobulin genes occurs after the onset of somatic mutation. Immunity 4: 241-250. (Pubitemid 26131007)
29. MacLennan IC (1994) Germinal centers. Annu Rev Immunol 12: 117-139.
30. Berek C, Berger A, Apel M (1991) Maturation of the immune response in germinal centers. Cell 67: 1121-1129. (Pubitemid 121001525)
31. Poholek AC, Hansen K, Hernandez SG, Eto D, Chandele A, et al. (2010) In vivo regulation of Bcl6 and T follicular helper cell development. J Immunol 185: 313-326.
32. Yang XY, Wang LH, Chen T, Hodge DR, Resau JH, et al. (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. (Pubitemid 30108833)
33. Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391: 82-86. (Pubitemid 28079219)
34. Ouyang W, Beckett O, Flavell RA, Li MO (2009) An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity 30: 358-371.
35. Xiong S, Salazar G, Patrushev N, Alexander RW (2011) FoxO1 mediates an autofeedback loop regulating SIRT1 expression. J Biol Chem 286: 5289-5299.
36. Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, et al. (2008) PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev 22: 2941-2952.
37. Su D, Coudriet GM, Hyun Kim D, Lu Y, Perdomo G, et al. (2009) FoxO1 links insulin resistance to proinflammatory cytokine IL-1beta production in macrophages. Diabetes 58: 2624-2633.
38. Baratelli F, Lin Y, Zhu L, Yang SC, Heuze-Vourc'h N, et al. (2005) Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J Immunol 175: 1483-1490. (Pubitemid 41023048)
39. Hontecillas R, 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. (Pubitemid 46333173)
40. Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, et al. (2008) A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 29: 127-137.
41. Walker LS, Gulbranson-Judge A, Flynn S, Brocker T, Raykundalia C, et al. (1999) Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers. J Exp Med 190: 1115-1122. (Pubitemid 29496504)
42. Akiba H, Takeda K, Kojima Y, Usui Y, Harada N, et al. (2005) The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo. J Immunol 175: 2340-2348. (Pubitemid 41113843)
43. Lane P, Burdet C, Hubele S, Scheidegger D, Muller U, et al. (1994) B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells. J Exp Med 179: 819-830. (Pubitemid 24065639)
44. Fazilleau N, McHeyzer-Williams LJ, Rosen H, McHeyzer-Williams MG (2009) The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol 10: 375-384.
45. Dowell P, Otto TC, Adi S, Lane MD (2003) Convergence of peroxisome proliferator-activated receptor gamma and Foxo1 signaling pathways. J Biol Chem 278: 45485-45491. (Pubitemid 37432687)