Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2016, Article ID 5393894, 9 pages
http://dx.doi.org/10.1155/2016/5393894
Review Article

CD4+ T Cell Fate in Glomerulonephritis: A Tale of Th1, Th17, and Novel Treg Subtypes

III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany

Received 6 December 2015; Revised 17 June 2016; Accepted 12 October 2016

Academic Editor: Jens Geginat

Copyright © 2016 Christan F. Krebs and Oliver M. Steinmetz. 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. W. G. Couser, “Basic and translational concepts of immune-mediated glomerular diseases,” Journal of the American Society of Nephrology, vol. 23, no. 3, pp. 381–399, 2012. View at Publisher · View at Google Scholar · View at Scopus
  2. C. Kurts, U. Panzer, H.-J. Anders, and A. J. Rees, “The immune system and kidney disease: basic concepts and clinical implications,” Nature Reviews Immunology, vol. 13, no. 10, pp. 738–753, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. P. G. Tipping and S. R. Holdsworth, “T cells in glomerulonephritis,” Springer Seminars in Immunopathology, vol. 24, no. 4, pp. 377–393, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. R. K. S. Phoon, A. R. Kitching, D. Odobasic, L. K. Jones, T. J. Semple, and S. R. Holdsworth, “T-bet deficiency attenuates renal injury in experimental crescentic glomerulonephritis,” Journal of the American Society of Nephrology, vol. 19, no. 3, pp. 477–485, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. H.-J. Paust, J.-E. Turner, O. M. Steinmetz et al., “The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis,” Journal of the American Society of Nephrology, vol. 20, no. 5, pp. 969–979, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. J.-E. Turner, H.-J. Paust, O. M. Steinmetz, and U. Panzer, “The Th17 immune response in renal inflammation,” Kidney International, vol. 77, no. 12, pp. 1070–1075, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. O. M. Steinmetz, S. A. Summers, P. Y. Gan, T. Semple, S. R. Holdsworth, and A. R. Kitching, “The Th17-defining transcription factor RORgammat promotes glomerulonephritis,” Journal of the American Society of Nephrology, vol. 22, no. 3, pp. 472–483, 2011. View at Publisher · View at Google Scholar
  8. S. Hünemörder, J. Treder, S. Ahrens et al., “TH1 and TH17 cells promote crescent formation in experimental autoimmune glomerulonephritis,” The Journal of Pathology, vol. 237, no. 1, pp. 62–71, 2015. View at Publisher · View at Google Scholar
  9. U. Panzer, O. M. Steinmetz, H.-J. Paust et al., “Chemokine receptor CXCR3 mediates T cell recruitment and tissue injury in nephrotoxic nephritis in mice,” Journal of the American Society of Nephrology, vol. 18, no. 7, pp. 2071–2084, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. O. M. Steinmetz, J.-E. Turner, H.-J. Paust et al., “CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis,” The Journal of Immunology, vol. 183, no. 7, pp. 4693–4704, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. J.-E. Turner, H.-J. Paust, O. M. Steinmetz et al., “CCR6 recruits regulatory T cells and Th17 cells to the kidney in glomerulonephritis,” Journal of the American Society of Nephrology, vol. 21, no. 6, pp. 974–985, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. H.-J. Paust, A. Ostmann, A. Erhardt et al., “Regulatory T cells control the Th1 immune response in murine crescentic glomerulonephritis,” Kidney International, vol. 80, no. 2, pp. 154–164, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. J. D. Ooi, S. L. Snelgrove, D. R. Engel et al., “Endogenous foxp3+ T-regulatory cells suppress anti-glomerular basement membrane nephritis,” Kidney International, vol. 79, no. 9, pp. 977–986, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. O. M. Steinmetz, J.-E. Turner, and U. Panzer, “Staying on top of things right from the start: the obsessive-compulsive disorder of regulatory T cells,” Journal of the American Society of Nephrology, vol. 21, no. 1, pp. 6–7, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Odobasic, P.-Y. Gan, S. A. Summers et al., “Interleukin-17A promotes early but attenuates established disease in crescentic glomerulonephritis in mice,” The American Journal of Pathology, vol. 179, no. 3, pp. 1188–1198, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. H.-J. Paust, J.-E. Turner, J.-H. Riedel et al., “Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis,” Kidney International, vol. 82, no. 1, pp. 72–83, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. M. A. Kluger, M. C. Meyer, A. Nosko et al., “RORγt+Foxp3+ cells are an independent bifunctional regulatory T cell lineage and mediate crescentic GN,” Journal of the American Society of Nephrology, vol. 27, no. 2, pp. 454–465, 2016. View at Publisher · View at Google Scholar
  18. D. Bending, H. De La Peña, M. Veldhoen et al., “Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice,” The Journal of Clinical Investigation, vol. 119, no. 3, pp. 565–572, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. K. Hirota, J. H. Duarte, M. Veldhoen et al., “Fate mapping of IL-17-producing T cells in inflammatory responses,” Nature Immunology, vol. 12, no. 3, pp. 255–263, 2011. View at Publisher · View at Google Scholar
  20. S. N. Harbour, C. L. Maynard, C. L. Zindl, T. R. Schoeb, and C. T. Weaver, “Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 22, pp. 7061–7066, 2015. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Jäger, V. Dardalhon, R. A. Sobel, E. Bettelli, and V. K. Kuchroo, “Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes,” Journal of Immunology, vol. 183, no. 11, pp. 7169–7177, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. H. J. Koenen, R. L. Smeets, P. M. Vink, E. van Rijssen, A. M. Boots, and I. Joosten, “Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells,” Blood, vol. 112, no. 6, pp. 2340–2352, 2008. View at Publisher · View at Google Scholar
  23. Y. K. Lee, H. Turner, C. L. Maynard et al., “Late developmental plasticity in the T helper 17 lineage,” Immunity, vol. 30, no. 1, pp. 92–107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Löhning, A. N. Hegazy, D. D. Pinschewer et al., “Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors,” Journal of Experimental Medicine, vol. 205, no. 1, pp. 53–61, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Lüthje, A. Kallies, Y. Shimohakamada et al., “The development and fate of follicular helper T cells defined by an IL-21 reporter mouse,” Nature Immunology, vol. 13, no. 5, pp. 491–498, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. X. O. Yang, R. Nurieva, G. J. Martinez et al., “Molecular antagonism and plasticity of regulatory and inflammatory T cell programs,” Immunity, vol. 29, no. 1, pp. 44–56, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. H. Ahlfors, P. J. Morrison, J. H. Duarte et al., “IL-22 fate reporter reveals origin and control of IL-22 production in homeostasis and infection,” Journal of Immunology, vol. 193, no. 9, pp. 4602–4613, 2014. View at Publisher · View at Google Scholar · View at Scopus
  28. C. Wilhelm, K. Hirota, B. Stieglitz et al., “An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation,” Nature Immunology, vol. 12, no. 11, pp. 1071–1077, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. X. Zhou, S. L. Bailey-Bucktrout, L. T. Jeker et al., “Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo,” Nature Immunology, vol. 10, no. 9, pp. 1000–1007, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. K. Hirota, J.-E. Turner, M. Villa et al., “Plasticity of TH 17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses,” Nature Immunology, vol. 14, no. 4, pp. 372–379, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. N. Gagliani, M. C. A. Vesely, A. Iseppon et al., “Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation,” Nature, vol. 523, no. 7559, pp. 221–225, 2015. View at Publisher · View at Google Scholar · View at Scopus
  32. J. T. Gaublomme, N. Yosef, Y. Lee et al., “Single-cell genomics unveils critical regulators of Th17 cell pathogenicity,” Cell, vol. 163, no. 6, pp. 1400–1412, 2015. View at Publisher · View at Google Scholar · View at Scopus
  33. C. Wang, N. Yosef, J. Gaublomme et al., “CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity,” Cell, vol. 163, no. 6, pp. 1413–1427, 2015. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Becattini, D. Latorre, F. Mele et al., “Functional heterogeneity of human memory CD4+ T cell clones primed by pathogens or vaccines,” Science, vol. 347, no. 6220, pp. 400–406, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Han, J. Glanville, L. Hansmann, and M. M. Davis, “Linking T-cell receptor sequence to functional phenotype at the single-cell level,” Nature Biotechnology, vol. 32, no. 7, pp. 684–692, 2014. View at Publisher · View at Google Scholar · View at Scopus
  36. M. DuPage and J. A. Bluestone, “Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease,” Nature Reviews Immunology, vol. 16, no. 3, pp. 149–163, 2016. View at Publisher · View at Google Scholar
  37. N. Komatsu, M. E. Mariotti-Ferrandiz, Y. Wang, B. Malissen, H. Waldmann, and S. Hori, “Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 6, pp. 1903–1908, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. N. Komatsu, K. Okamoto, S. Sawa et al., “Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis,” Nature Medicine, vol. 20, no. 1, pp. 62–68, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Valmori, C. Raffin, I. Raimbaud, and M. Ayyoub, “Human RORgammat+TH17 cells preferentially differentiate from naive FOXP3+Treg in the presence of lineage-specific polarizing factors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 45, pp. 19402–19407, 2010. View at Google Scholar
  40. E. Yurchenko, M. T. Shio, T. C. Huang et al., “Inflammation-driven reprogramming of CD4+Foxp3+ regulatory T cells into pathogenic Th1/Th17 T effectors is abrogated by mTOR inhibition in vivo,” PLoS ONE, vol. 7, no. 4, Article ID e35572, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. A. R. Kitching and S. R. Holdsworth, “The emergence of Th17 cells as effectors of renal injury,” Journal of the American Society of Nephrology, vol. 22, no. 2, pp. 235–238, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. S. A. Summers, O. M. Steinmetz, M. Li et al., “Th1 and Th17 cells induce proliferative glomerulonephritis,” Journal of the American Society of Nephrology, vol. 20, no. 12, pp. 2518–2524, 2009. View at Publisher · View at Google Scholar
  43. C. Tulone, A. Giorgini, S. Freeley, A. Coughlan, and M. G. Robson, “Transferred antigen-specific TH17 but not TH1 cells induce crescentic glomerulonephritis in mice,” The American Journal of Pathology, vol. 179, no. 6, pp. 2683–2690, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. C. F. Krebs, J. E. Turner, H. J. Paust et al., “Plasticity of Th17 cells in autoimmune kidney diseases,” The Journal of Immunology, vol. 197, no. 2, pp. 449–457, 2016. View at Publisher · View at Google Scholar
  45. E. Esplugues, S. Huber, N. Gagliani et al., “Control of TH17 cells occurs in the small intestine,” Nature, vol. 475, no. 7357, pp. 514–518, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Huber, N. Gagliani, E. Esplugues et al., “Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner,” Immunity, vol. 34, no. 4, pp. 554–565, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. J. H. Duarte, S. Zelenay, M.-L. Bergman, A. C. Martins, and J. Demengeot, “Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions,” European Journal of Immunology, vol. 39, no. 4, pp. 948–955, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. S. L. Bailey-Bucktrout, M. Martinez-Llordella, X. Zhou et al., “Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response,” Immunity, vol. 39, no. 5, pp. 949–962, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Miyao, S. Floess, R. Setoguchi et al., “Plasticity of Foxp3+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells,” Immunity, vol. 36, no. 2, pp. 262–275, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. Y. P. Rubtsov, R. E. Niec, S. Josefowicz et al., “Stability of the regulatory T cell lineage in vivo,” Science, vol. 329, no. 5999, pp. 1667–1671, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Hori, “Lineage stability and phenotypic plasticity of Foxp3+ regulatory T cells,” Immunological Reviews, vol. 259, no. 1, pp. 159–172, 2014. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Chaudhry, D. Rudra, P. Treuting et al., “CD4+ regulatory T cells control TH17 responses in a stat3-dependent manner,” Science, vol. 326, no. 5955, pp. 986–991, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. M. A. Koch, G. Tucker-Heard, N. R. Perdue, J. R. Killebrew, K. B. Urdahl, and D. J. Campbell, “The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation,” Nature Immunology, vol. 10, no. 6, pp. 595–602, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Lochner, L. Peduto, M. Cherrier et al., “In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells,” The Journal of Experimental Medicine, vol. 205, no. 6, pp. 1381–1393, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. D. Q. Tran, H. Ramsey, and E. M. Shevach, “Induction of FOXP3 expression in naive human CD4+FOXP3 - T cells by T-cell receptor stimulation is transforming growth factor-β-dependent but does not confer a regulatory phenotype,” Blood, vol. 110, no. 8, pp. 2983–2990, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Wang, A. Ioan-Facsinay, E. I. H. van der Voort, T. W. J. Huizinga, and R. E. M. Toes, “Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells,” European Journal of Immunology, vol. 37, no. 1, pp. 129–138, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. M. A. Kluger, M. Luig, C. Wegscheid et al., “Stat3 programs Th17-specific regulatory T cells to control GN,” Journal of the American Society of Nephrology, vol. 25, no. 6, pp. 1291–1302, 2014. View at Publisher · View at Google Scholar · View at Scopus
  58. M. A. Kluger, S. Melderis, A. Nosko et al., “Treg17 cells are programmed by Stat3 to suppress Th17 responses in systemic lupus,” Kidney International, vol. 89, no. 1, pp. 158–166, 2016. View at Publisher · View at Google Scholar · View at Scopus
  59. H. J. Paust, J. H. Riedel, C. F. Krebs et al., “CXCR3+ regulatory T cells control TH1 responses in crescentic GN,” Journal of the American Society of Nephrology, vol. 27, no. 7, pp. 1933–1942, 2016. View at Publisher · View at Google Scholar
  60. A. Nosko, M. A. Kluger, P. Diefenhardt et al., “T-Bet enhances regulatory T cell fitness and directs control of Th1 responses in crescentic GN,” Journal of the American Society of Nephrology, 2016. View at Publisher · View at Google Scholar
  61. D. J. Campbell and M. A. Koch, “Phenotypical and functional specialization of FOXP3+ regulatory T cells,” Nature Reviews Immunology, vol. 11, no. 2, pp. 119–130, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Chaudhry and A. Y. Rudensky, “Control of inflammation by integration of environmental cues by regulatory T cells,” The Journal of Clinical Investigation, vol. 123, no. 3, pp. 939–944, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Liston and D. H. D. Gray, “Homeostatic control of regulatory T cell diversity,” Nature Reviews Immunology, vol. 14, no. 3, pp. 154–165, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Ohnmacht, J.-H. Park, S. Cording et al., “The microbiota regulates type 2 immunity through RORγt(+) T cells,” Science, vol. 349, no. 6251, pp. 989–993, 2015. View at Publisher · View at Google Scholar · View at Scopus
  65. E. Sefik, N. Geva-Zatorsky, S. Oh et al., “Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells,” Science, vol. 349, no. 6251, pp. 993–997, 2015. View at Publisher · View at Google Scholar
  66. A. M. Pesenacker, D. Bending, S. Ursu, Q. Wu, K. Nistala, and L. R. Wedderburn, “CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines,” Blood, vol. 121, no. 14, pp. 2647–2658, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. N. R. Blatner, M. F. Mulcahy, K. L. Dennis et al., “Expression of RORgammat marks a pathogenic regulatory T cell subset in human colon cancer,” Science Translational Medicine, vol. 4, no. 164, Article ID 164ra159, 2012. View at Publisher · View at Google Scholar
  68. M. Ayyoub, F. Deknuydt, I. Raimbaud et al., “Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the TH17 lineage-specific transcription factor RORγt,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 21, pp. 8635–8640, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. B. H. Yang, S. Hagemann, P. Mamareli et al., “Foxp3+ T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation,” Mucosal Immunology, vol. 9, no. 2, pp. 444–457, 2015. View at Publisher · View at Google Scholar