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Journal of Immunology Research
Volume 2015, Article ID 837859, 15 pages
http://dx.doi.org/10.1155/2015/837859
Research Article

Inhibins Tune the Thymocyte Selection Process by Regulating Thymic Stromal Cell Differentiation

Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico

Received 26 September 2014; Revised 15 January 2015; Accepted 20 January 2015

Academic Editor: Oscar Bottasso

Copyright © 2015 Ebzadrel Carbajal-Franco et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Licona-Limón and G. Soldevila, “The role of TGF-beta superfamily during T cell development: new insights,” Immunology Letters, vol. 109, no. 1, pp. 1–12, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. M. M. Matzuk, M. J. Finegold, J.-G. J. Su, A. J. W. Hsueh, and A. Bradley, “Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice,” Nature, vol. 360, no. 6402, pp. 313–319, 1992. View at Publisher · View at Google Scholar · View at Scopus
  3. M. M. Matzuk, M. J. Finegold, J. P. Mather, L. Krummen, H. Lu, and A. Bradley, “Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 19, pp. 8817–8821, 1994. View at Publisher · View at Google Scholar · View at Scopus
  4. D. J. Phillips and T. K. Woodruff, “Inhibin: actions and signalling,” Growth Factors, vol. 22, no. 1, pp. 13–18, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. G. R. Aleman-Muench and G. Soldevila, “When versatility matters: activins/inhibins as key regulators of immunity,” Immunology and Cell Biology, vol. 90, no. 2, pp. 137–148, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. M. P. Hedger, W. R. Winnall, D. J. Phillips, and D. M. de Kretser, “The regulation and functions of activin and follistatin in inflammation and immunity,” Vitamins & Hormones, vol. 85, pp. 255–297, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. S. E. Segerer, N. Müller, J. Van den Brandt et al., “The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation,” Reproductive Biology and Endocrinology, vol. 6, article 17, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. Takahama, “Journey through the thymus: stromal guides for T-cell development and selection,” Nature Reviews Immunology, vol. 6, no. 2, pp. 127–135, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Boehm and C. C. Bleul, “Thymus-homing precursors and the thymic microenvironment,” Trends in Immunology, vol. 27, no. 10, pp. 477–484, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. E. F. Lind, S. E. Prockop, H. E. Porritt, and H. T. Petrie, “Mapping precursor movement through the postnatal thymus reveals specific microenvironments supporting defined stages of early lymphoid development,” The Journal of Experimental Medicine, vol. 194, no. 2, pp. 127–134, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. R. Ceredig and T. Rolink, “A positive look at double-negative thymocytes,” Nature Reviews Immunology, vol. 2, no. 11, pp. 888–897, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. H. T. Petrie and J. C. Zúñiga-Pflücker, “Zoned out: functional mapping of stromal signaling microenvironments in the thymus,” Annual Review of Immunology, vol. 25, pp. 649–679, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Singer, S. Adoro, and J. H. Park, “Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice,” Nature Reviews Immunology, vol. 8, no. 10, pp. 788–801, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Baik, E. J. Jenkinson, P. J. L. Lane, G. Anderson, and W. E. Jenkinson, “Generation of both cortical and Aire+ medullary thymic epithelial compartments from CD205+ progenitors,” European Journal of Immunology, vol. 43, no. 3, pp. 589–594, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Akiyama, M. Shinzawa, and N. Akiyama, “TNF receptor family signaling in the development and functions of medullary thymic epithelial cells,” Frontiers in Immunology, vol. 3, article 278, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Shortman and W. R. Heath, “The CD8+ dendritic cell subset,” Immunological Reviews, vol. 234, no. 1, pp. 18–31, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. L. Klein, B. Kyewski, P. M. Allen, and K. A. Hogquist, “Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see),” Nature Reviews Immunology, vol. 14, no. 6, pp. 377–391, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. H. Hadeiba and E. C. Butcher, “Thymus-homing dendritic cells in central tolerance,” European Journal of Immunology, vol. 43, no. 6, pp. 1425–1429, 2013. View at Publisher · View at Google Scholar · View at Scopus
  19. E. M. Shevach, R. A. DiPaolo, J. Andersson, D.-M. Zhao, G. L. Stephens, and A. M. Thornton, “The lifestyle of naturally occurring CD4+CD25+Foxp3+ regulatory T cells,” Immunological Reviews, vol. 212, pp. 60–73, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. H. Hadeiba, K. Lahl, A. Edalati et al., “Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance,” Immunity, vol. 36, no. 3, pp. 438–450, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. E. Martín-Gayo, E. Sierra-Filardi, A. L. Corbí, and M. L. Toribio, “Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development,” Blood, vol. 115, no. 26, pp. 5366–5375, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. C. D. Surh and J. Sprent, “T-cell apoptosis detected in situ during positive and negative selection in the thymus,” Nature, vol. 372, no. 6501, pp. 100–103, 1994. View at Publisher · View at Google Scholar · View at Scopus
  23. Z. Szondy, É. Garabuczi, K. Tóth, B. Kiss, and K. Köröskényi, “Thymocyte death by neglect: contribution of engulfing macrophages,” European Journal of Immunology, vol. 42, no. 7, pp. 1662–1667, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. P. Licona, J. Chimal-Monroy, and G. Soldevila, “Inhibins are the major activin ligands expressed during early thymocyte development,” Developmental Dynamics, vol. 235, no. 4, pp. 1124–1132, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. P. Licona-Limón, G. Alemán-Muench, J. Chimal-Monroy et al., “Activins and inhibins: novel regulators of thymocyte development,” Biochemical and Biophysical Research Communications, vol. 381, no. 2, pp. 229–235, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Rosendahl, M. Speletas, K. Leandersson, F. Ivars, and P. Sideras, “Transforming growth factor-β- and activin-Smad signaling pathways are activated at distinct maturation stages of the thymopoeisis,” International Immunology, vol. 15, no. 12, pp. 1401–1414, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. D. H. D. Gray, A. L. Fletcher, M. Hammett et al., “Unbiased analysis, enrichment and purification of thymic stromal cells,” Journal of Immunological Methods, vol. 329, no. 1-2, pp. 56–66, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. W. Shou, T. K. Woodruff, and M. M. Matzuk, “Role of androgens in testicular tumor development in inhibin-deficient mice,” Endocrinology, vol. 138, no. 11, pp. 5000–5005, 1997. View at Publisher · View at Google Scholar · View at Scopus
  29. S. J. Yang, S. Ahn, C. S. Park et al., “The quantitative assessment of MHC II on thymic epithelium: Implications in cortical thymocyte development,” International Immunology, vol. 18, no. 5, pp. 729–739, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. N. R. Manley, E. R. Richie, C. C. Blackburn, B. G. Condie, and J. Sage, “Structure and function of the thymic microenvironment,” Frontiers in Bioscience, vol. 16, no. 7, pp. 2461–2477, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. L. Wu and K. Shortman, “Heterogeneity of thymic dendritic cells,” Seminars in Immunology, vol. 17, no. 4, pp. 304–312, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Wu and Y.-J. Liu, “Development of dendritic-cell lineages,” Immunity, vol. 26, no. 6, pp. 741–750, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. G. L. Stritesky, S. C. Jameson, and K. A. Hogquist, “Selection of self-reactive T cells in the thymus,” Annual Review of Immunology, vol. 30, pp. 95–114, 2012. View at Publisher · View at Google Scholar · View at Scopus
  34. X. J. Zhang, Y. Li, G. X. Tai et al., “Effects of activin A on the activities of the mouse peritoneal macrophages.,” Cellular & Molecular Immunology, vol. 2, no. 1, pp. 63–67, 2005. View at Google Scholar · View at Scopus
  35. J. Zhou, G. Tai, H. Liu et al., “Activin A down-regulates the phagocytosis of lipopolysaccharide-activated mouse peritoneal macrophages in vitro and in vivo,” Cellular Immunology, vol. 255, no. 1-2, pp. 69–75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. R. M. Nüsing and J. Barsig, “Induction of prostanoid, nitric oxide, and cytokine formation in rat bone marrow derived macrophages by activin A,” British Journal of Pharmacology, vol. 127, no. 4, pp. 919–926, 1999. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Dakic, Q.-X. Shao, A. D'Amico et al., “Development of the dendritic cell system during mouse ontogeny,” The Journal of Immunology, vol. 172, no. 2, pp. 1018–1027, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. S. L. van Dommelen, A. Rizzitelli, A. Chidgey, R. Boyd, K. Shortman, and L. Wu, “Regeneration of dendritic cells in aged mice,” Cellular and Molecular Immunology, vol. 7, no. 2, pp. 108–115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. L. Klein, M. Hinterberger, G. Wirnsberger, and B. Kyewski, “Antigen presentation in the thymus for positive selection and central tolerance induction,” Nature Reviews Immunology, vol. 9, no. 12, pp. 833–844, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. T. Okada, Z.-X. Lian, M. Naiki, A. A. Ansari, S. Ikehara, and M. E. Gershwin, “Murine thymic plasmacytoid dendritic cells,” European Journal of Immunology, vol. 33, no. 4, pp. 1012–1019, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. S. LeibundGut-Landmann, J.-M. Waldburger, C. Reis e Sousa, H. Acha-Orbea, and W. Reith, “MHC class II expression is differentially regulated in plasmacytoid and conventional dendritic cells,” Nature Immunology, vol. 5, no. 9, pp. 899–908, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Moore, D. Sauma, J. Morales, M. R. Bono, M. Rosemblatt, and J. A. Fierro, “Transforming growth factor-beta and all-trans retinoic acid generate ex vivo transgenic regulatory T cells with intestinal homing receptors,” Transplantation Proceedings, vol. 41, no. 6, pp. 2670–2672, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. E. Sierra-Filardi, C. Nieto, Á. Domínguez-Soto et al., “CCL2 shapes macrophage polarization by GM-CSF and M-CSF: identification of CCL2/CCR2-dependent gene expression profile,” Journal of Immunology, vol. 192, no. 8, pp. 3858–3867, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Salogni, T. Musso, D. Bosisio et al., “Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14,” Blood, vol. 113, no. 23, pp. 5848–5856, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Musso, S. Scutera, W. Vermi et al., “Activin A induces langerhans cell differentiation in vitro and in human skin explants,” PLoS ONE, vol. 3, no. 9, Article ID e3271, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. N. C. Robson, D. J. Phillips, T. McAlpine et al., “Activin-A: a novel dendritic cell derived cytokine that potently attenuates CD40 ligand specific cytokine and chemokine production,” Blood, vol. 111, no. 5, pp. 2733–2743, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. M. D. Bunting, I. Comerford, N. Seach et al., “CCX-CKR deficiency alters thymic stroma impairing thymocyte development and promoting autoimmunity,” Blood, vol. 121, no. 1, pp. 118–128, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. S. W. Rossi, W. E. Jenkinson, G. Anderson, and E. J. Jenkinson, “Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium,” Nature, vol. 441, no. 7096, pp. 988–991, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Hauri-Hohl, S. Zuklys, G. A. Holländer, and S. F. Ziegler, “A regulatory role for TGF-β signaling in the establishment and function of the thymic medulla,” Nature Immunology, vol. 15, no. 6, pp. 554–561, 2014. View at Publisher · View at Google Scholar · View at Scopus
  50. K. Wong, N. L. Lister, M. Barsanti et al., “Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus,” Cell Reports, vol. 8, no. 4, pp. 1198–1209, 2014. View at Publisher · View at Google Scholar
  51. K. Takada, I. Ohigashi, M. Kasai, H. Nakase, and Y. Takahama, “Development and function of cortical thymic epithelial cells,” Current Topics in Microbiology and Immunology, vol. 373, pp. 1–17, 2014. View at Google Scholar · View at Scopus
  52. Y. Xia and A. L. Schneyer, “The biology of activin: recent advances in structure, regulation and function,” The Journal of Endocrinology, vol. 202, no. 1, pp. 1–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. S. C. Cipriano, L. Chen, T. R. Kumar, and M. M. Matzuk, “Follistatin is a modulator of gonadal tumor progression and the activin-induced wasting syndrome in inhibin-deficient mice,” Endocrinology, vol. 141, no. 7, pp. 2319–2327, 2000. View at Publisher · View at Google Scholar · View at Scopus
  54. M. M. Matzuk and A. Bradley, “Identification and analysis of tumor suppressor genes using transgenic mouse models,” Seminars in Cancer Biology, vol. 5, no. 1, pp. 37–45, 1994. View at Google Scholar · View at Scopus
  55. S. Huber, F. R. Stahl, J. Schrader et al., “Activin a promotes the TGF-beta-induced conversion of CD4+CD25- T cells into Foxp3+ induced regulatory T cells,” Journal of Immunology, vol. 182, no. 8, pp. 4633–4640, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. D. M. Simons, C. C. Picca, S. Oh et al., “How specificity for self-peptides shapes the development and function of regulatory T cells,” Journal of Leukocyte Biology, vol. 88, no. 6, pp. 1099–1107, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. K. A. Hogquist and S. C. Jameson, “The self-obsession of T cells: how TCR signaling thresholds affect fate ‘decisions’ and effector function,” Nature Immunology, vol. 15, no. 9, pp. 815–823, 2014. View at Publisher · View at Google Scholar
  58. F. Ramsdell, J. C. Zuniga-Pflucker, and Y. Takahama, “In vitro systems for the study of T cell development: fetal thymus organ culture and OP9-DL1 cell coculture,” Current Protocols in Immunology, chapter 3, unit 3 18, 2006. View at Google Scholar
  59. J. M. Waldburger, T. Suter, A. Fontana, H. Acha-Orbea, and W. Reith, “Selective abrogation of major histocompatibility complex class II expression on extrahematopoietic cells in mice lacking promoter IV of the class II transactivator gene,” The Journal of Experimental Medicine, vol. 194, no. 4, pp. 393–406, 2001. View at Publisher · View at Google Scholar · View at Scopus
  60. T. Nakagawa, W. Roth, P. Wong et al., “Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus,” Science, vol. 280, no. 5362, pp. 450–453, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. K. Honey, T. Nakagawa, C. Peters, and A. Rudensky, “Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands,” The Journal of Experimental Medicine, vol. 195, no. 10, pp. 1349–1358, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. G. Wirnsberger, M. Hinterberger, and L. Klein, “Regulatory T-cell differentiation versus clonal deletion of autoreactive thymocytes,” Immunology and Cell Biology, vol. 89, no. 1, pp. 45–53, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Hinterberger, M. Aichinger, O. P. da Costa, D. Voehringer, R. Hoffmann, and L. Klein, “Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance,” Nature Immunology, vol. 11, no. 6, pp. 512–519, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. D. F. Atibalentja, C. A. Byersdorfer, and E. R. Unanue, “Thymus-blood protein interactions are highly effective in negative selection and regulatory T cell induction,” Journal of Immunology, vol. 183, no. 12, pp. 7909–7918, 2009. View at Google Scholar · View at Scopus