The vitamin D analog, TX527, promotes a human CD4+CD25 highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation

Journal of Immunology

Volumn 186, Issue 1, 2011, Pages 132-142

  Baeke, Femke ^a   Korf, Hannelie ^a   Overbergh, Lut ^a   Verstuyf, Annemieke ^a   Thorrez, Lieven ^a   Van Lommel, Leentje ^a   Waer, Mark ^a   Schuit, Frans ^a   Gysemans, Conny ^a   Mathieu, Chantal ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

CD3 ANTIGEN; CD4 ANTIGEN; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR4; CYTOKINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; HOMING RECEPTOR; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 4; INTERLEUKIN 7 RECEPTOR; L SELECTIN; OX40 LIGAND; TX 527; UNCLASSIFIED DRUG; VITAMIN D DERIVATIVE;

ARTICLE; CD3+ T LYMPHOCYTE; CD4+ CD25+ CD127+ T LYMPHOCYTE; CD4+ CD25+ T LYMPHOCYTE; CELL ACTIVATION; CELL CULTURE; CELL DIFFERENTIATION; CELL MIGRATION; CONTROLLED STUDY; DIFFERENTIAL DISPLAY; EFFECTOR CELL; FUNCTIONAL STATUS; GENE EXPRESSION; HUMAN; INFLAMMATION; LYMPHOID ORGAN; MICROARRAY ANALYSIS; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ALKYNES; ANTIGENS, CD3; CD8-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; CELLS, CULTURED; CHEMOTAXIS, LEUKOCYTE; CHOLECALCIFEROL; EPITOPES, T-LYMPHOCYTE; GENE EXPRESSION REGULATION; GROWTH INHIBITORS; HUMANS; INFLAMMATION MEDIATORS; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; INTERLEUKIN-7 RECEPTOR ALPHA SUBUNIT; LYMPHOCYTE ACTIVATION; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; RECEPTORS, CCR10; RECEPTORS, CCR4; RECEPTORS, CCR5; RECEPTORS, CHEMOKINE; RECEPTORS, CXCR3; RECEPTORS, VIRUS; T-LYMPHOCYTES, REGULATORY; TRANSCRIPTION, GENETIC;

EID: 79251567975     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1000695     Document Type: Article

References (43)

1. Adams, J. S., and M. Hewison. 2008. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat. Clin. Pract. Endocrinol. Metab. 4: 80-90.
2. Baeke, F., E. van Etten, C. Gysemans, L. Overbergh, and C. Mathieu. 2008. Vitamin D signaling in immune-mediated disorders: Evolving insights and therapeutic opportunities. Mol. Aspects Med. 29: 376-387.
3. Adorini, L., and G. Penna. 2009. Dendritic cell tolerogenicity: a key mechanism in immunomodulation by vitamin D receptor agonists. Hum. Immunol. 70: 345-352.
4. Adorini, L., G. Penna, N. Giarratana, A. Roncari, S. Amuchastegui, K. C. Daniel, and M. Uskokovic. 2004. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J. Steroid Biochem. Mol. Biol. 89-90: 437-441.
5. Penna, G., and L. Adorini. 2000. 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 164: 2405-2411.
6. van Halteren, A. G., E. van Etten, E. C. de Jong, R. Bouillon, B. O. Roep, and C. Mathieu. 2002. Redirection of human autoreactive T-cells Upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D (3). Diabetes 51: 2119-2125.
7. Penna, G., A. Roncari, S. Amuchastegui, K. C. Daniel, E. Berti, M. Colonna, and L. Adorini. 2005. Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3. Blood 106: 3490-3497.
8. Veldman, C. M., M. T. Cantorna, and H. F. DeLuca. 2000. Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch. Biochem. Biophys. 374: 334-338.
9. Rigby, W. F., T. Stacy, and M. W. Fanger. 1984. Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol). J. Clin. Invest. 74: 1451-1455.
10. Bhalla, A. K., E. P. Amento, B. Serog, and L. H. Glimcher. 1984. 1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J. Immunol. 133: 1748-1754.
11. Boonstra, A., F. J. Barrat, C. Crain, V. L. Heath, H. F. Savelkoul, and A. O'Garra. 2001. 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J. Immunol. 167: 4974-4980.
12. Staeva-Vieira, T. P., and L. P. Freedman. 2002. 1,25-dihydroxyvitamin D3 inhibits IFN-gamma and IL-4 levels during in vitro polarization of primary murine CD4+ T cells. J. Immunol. 168: 1181-1189.
13. Mahon, B. D., A. Wittke, V. Weaver, and M. T. Cantorna. 2003. The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J. Cell. Biochem. 89: 922-932.
14. Jeffery, L. E., F. Burke, M. Mura, Y. Zheng, O. S. Qureshi, M. Hewison, L. S. Walker, D. A. Lammas, K. Raza, and D. M. Sansom. 2009. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J. Immunol. 183: 5458-5467.
15. Mortensen, J. T., J. Lichtenberg, and L. Binderup. 1996. Toxicity of 1,25-dihydroxyvitamin D3, tacalcitol, and calcipotriol after topical treatment in rats. J. Investig. Dermatol. Symp. Proc. 1: 60-63.
16. Van Etten, E., B. Decallonne, L. Verlinden, A. Verstuyf, R. Bouillon, and C. Mathieu. 2003. Analogs of 1alpha,25-dihydroxyvitamin D3 as pluripotent immunomodulators. J. Cell. Biochem. 88: 223-226.
17. Baeke, F., H. Korf, L. Overbergh, E. van Etten, A. Verstuyf, C. Gysemans, and C. Mathieu. 2010. Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system. J. Steroid Biochem. Mol. Biol. 121: 221-227.
18. Freudenberg, J. M., V. K. Joshi, Z. Hu, and M. Medvedovic. 2009. CLEAN: CLustering Enrichment ANalysis. BMC Bioinformatics 10: 234-249.
19. Overbergh, L., A. Giulietti, D. Valckx, R. Decallonne, R. Bouillon, and C. Mathieu. 2003. The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression. J. Biomol. Tech. 14: 33-43.
20. Giulietti, A., L. Overbergh, D. Valckx, B. Decallonne, R. Bouillon, and C. Mathieu. 2001. An overview of real-time quantitative PCR: applications to quantify cytokine gene expression. Methods 25: 386-401. (Pubitemid 34164011)
21. Stoffels, K., L. Overbergh, A. Giulietti, L. Verlinden, R. Bouillon, and C. Mathieu. 2006. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J. Bone Miner. Res. 21: 37-47.
22. Bullens, D. M., E. Truyen, L. Coteur, E. Dilissen, P. W. Hellings, L. J. Dupont, and J. L. Ceuppens. 2006. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir. Res. 7: 135-144.
23. Bouillon, R., A. Verstuyf, L. Verlinden, G. Eelen, and C. Mathieu. 2003. Prospects for vitamin D receptor modulators as candidate drugs for cancer and (auto) immune diseases. Recent Results Cancer Res. 164: 353-356.
24. Rigby, W. F., B. Yirinec, R. L. Oldershaw, and M. W. Fanger. 1987. Comparison of the effects of 1,25-dihydroxyvitamin D3 on T lymphocyte subpopulations. Eur. J. Immunol. 17: 563-566.
25. Lemire, J. M., J. S. Adams, V. Kermani-Arab, A. C. Bakke, R. Sakai, and S. C. Jordan. 1985. 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J. Immunol. 134: 3032-3035.
26. Correale, J., M. C. Ysrraelit, and M. I. Gaitán. 2009. Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132: 1146-1160.
27. Barrat, F. J., D. J. Cua, A. Boonstra, D. F. Richards, C. Crain, H. F. Savelkoul, R. de Waal-Malefyt, R. L. Coffman, C. M. Hawrylowicz, and A. O'Garra. 2002. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)-and Th2-inducing cytokines. J. Exp. Med. 195: 603-616.
28. Borgogni, E., E. Sarchielli, M. Sottili, V. Santarlasci, L. Cosmi, S. Gelmini, A. Lombardi, G. Cantini, G. Perigli, M. Luconi, et al. 2008. Elocalcitol inhibits inflammatory responses in human thyroid cells and T cells. Endocrinology 149: 3626-3634.
29. Bartels, L. E., S. P. Jørgensen, J. Agnholt, J. Kelsen, C. L. Hvas, and J. F. Dahlerup. 2007. 1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease. Int. Immunopharmacol. 7: 1755-1764.
30. Mosser, D. M., and X. Zhang. 2008. Interleukin-10: new perspectives on an old cytokine. Immunol. Rev. 226: 205-218.
31. Urry, Z., E. Xystrakis, D. F. Richards, J. McDonald, Z. Sattar, D. J. Cousins, C. J. Corrigan, E. Hickman, Z. Brown, and C. M. Hawrylowicz. 2009. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1alpha,25- dihydroxyvitamin D3 abrogates regulatory function. J. Clin. Invest. 119: 387-398.
32. Spach, K. M., F. E. Nashold, B. N. Dittel, and C. E. Hayes. 2006. IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J. Immunol. 177: 6030-6037.
33. Vieira, P. L., J. R. Christensen, S. Minaee, E. J. O'Neill, F. J. Barrat, A. Boonstra, T. Barthlott, B. Stockinger, D. C. Wraith, and A. O'Garra. 2004. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J. Immunol. 172: 5986-5993.
34. Gregori, S., N. Giarratana, S. Smiroldo, M. Uskokovic, and L. Adorini. 2002. A 1alpha,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes 51: 1367-1374.
35. Ghoreishi, M., P. Bach, J. Obst, M. Komba, J. C. Fleet, and J. P. Dutz. 2009. Expansion of antigen-specific regulatory T cells with the topical vitamin d analog calcipotriol. J. Immunol. 182: 6071-6078.
36. Rigby, W. F., B. J. Hamilton, and M. G. Waugh. 1990. 1,25- Dihydroxyvitamin D3 modulates the effects of interleukin 2 independent of IL-2 receptor binding. Cell. Immunol. 125: 396-414.
37. Qu, Y., and Y. Zhao. 2007. Regulatory CD4(+)CD25(+) T-cells are controlled by multiple pathways at multiple levels. Int. Rev. Immunol. 26: 145-160.
38. Sigmundsdottir, H., J. Pan, G. F. Debes, C. Alt, A. Habtezion, D. Soler, and E. C. Butcher. 2007. DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27. Nat. Immunol. 8: 285-293.
39. Yamanaka, K., C. J. Dimitroff, R. C. Fuhlbrigge, M. Kakeda, I. Kurokawa, H. Mizutani, and T. S. Kupper. 2008. Vitamins A and D are potent inhibitors of cutaneous lymphocyte-associated antigen expression. J. Allergy Clin. Immunol. 121: 148-157, e3.
40. Kondo, T., and M. Takiguchi. 2009. Human memory CCR4+CD8+ T cell subset has the ability to produce multiple cytokines. Int. Immunol. 21: 523-532.
41. Topilski, I., L. Flaishon, Y. Naveh, A. Harmelin, Y. Levo, and I. Shachar. 2004. The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing. Eur. J. Immunol. 34: 1068-1076.
42. D'Ambrosio, D., P. Panina-Bordignon, and F. Sinigaglia. 2003. Chemokine receptors in inflammation: an overview. J. Immunol. Methods 273: 3-13.
43. Duhen, T., R. Geiger, D. Jarrossay, A. Lanzavecchia, and F. Sallusto. 2009. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat. Immunol. 10: 857-863.