IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Osteopontin Potentiates Pulmonary Inflammation and Fibrosis by Modulating IL-17/IFN-γ-secreting T-cell Ratios in Bleomycin-treated Mice

  • Oh, Keunhee (Laboratory of Immunology and Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Seo, Myung Won (Laboratory of Immunology and Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Kim, Young Whan (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Lee, Dong-Sup (Laboratory of Immunology and Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine)
  • Received : 2015.03.27
  • Accepted : 2015.06.05
  • Published : 2015.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPNdeficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and IL-17-producing ${\gamma}{\delta}$ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and the percentage of IFN-$\gamma$-producing ${\gamma}{\delta}$ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in $CD4^+$ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-$\gamma$ T cells.

Keywords

References

  1. Wynn, T. A., and T. R. Ramalingam. 2012. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat. Med. 18: 1028-1040. https://doi.org/10.1038/nm.2807
  2. Wynn, T. A. 2011. Integrating mechanisms of pulmonary fibrosis. J. Exp. Med. 208: 1339-1350. https://doi.org/10.1084/jem.20110551
  3. Wick, G., C. Grundtman, C. Mayerl, T. F. Wimpissinger, J. Feichtinger, B. Zelger, R. Sgonc, and D. Wolfram. 2013. The immunology of fibrosis. Annu. Rev. Immunol. 31: 107-135. https://doi.org/10.1146/annurev-immunol-032712-095937
  4. Lo Re, S., L. Dumoutier, I. Couillin, C. Van Vyve, Y. Yakoub, F. Uwambayinema, B. Marien, S. van den Brule, J. Van Snick, C. Uyttenhove, B. Ryffel, J. C. Renauld, D. Lison, and F. Huaux. 2010. IL-17A-producing gammadelta T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis. J. Immunol. 184: 6367-6377. https://doi.org/10.4049/jimmunol.0900459
  5. Sonnenberg, G. F., M. G. Nair, T. J. Kirn, C. Zaph, L. A. Fouser, and D. Artis. 2010. Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. J. Exp. Med. 207: 1293-12305. https://doi.org/10.1084/jem.20092054
  6. Wilson, M. S., S. K. Madala, T. R. Ramalingam, B. R. Gochuico, I. O. Rosas, A. W. Cheever, and T. A. Wynn. 2010. Bleomycin and IL-1beta-mediated pulmonary fibrosis is IL-17A dependent. J. Exp. Med. 207: 535-552. https://doi.org/10.1084/jem.20092121
  7. Oh, K., H. B. Park, O. J. Byoun, D. M. Shin, E. M. Jeong, Y. W. Kim, Y. S. Kim, G. Melino, I. G. Kim, and D. S. Lee. 2011. Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice. J. Exp. Med. 208: 1707-1719. https://doi.org/10.1084/jem.20101457
  8. Ishijima, M., S. R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D. T. Denhardt, and M. Noda. 2001. Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin. J. Exp. Med. 193: 399-404. https://doi.org/10.1084/jem.193.3.399
  9. Wang, K. X., and D. T. Denhardt. 2008. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev. 19: 333-345. https://doi.org/10.1016/j.cytogfr.2008.08.001
  10. Chakraborty, G., S. Jain, and G. C. Kundu. 2008. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res. 68: 152-161. https://doi.org/10.1158/0008-5472.CAN-07-2126
  11. Ahmed, M., R. Behera, G. Chakraborty, S. Jain, V. Kumar, P. Sharma, A. Bulbule, S. Kale, S. Kumar, R. Mishra, R. Raja, S. Saraswati, R. Kaur, G. Soundararajan, D. Kumar, D. Thorat, M. Sanyal, A. Ramdasi, P. Ghosh, and G. C. Kundu. 2011. Osteopontin: a potentially important therapeutic target in cancer. Expert Opin. Ther. Targets 15: 1113-1126. https://doi.org/10.1517/14728222.2011.594438
  12. Yamamoto, N., F. Sakai, S. Kon, J. Morimoto, C. Kimura, H. Yamazaki, I. Okazaki, N. Seki, T. Fujii, and T. Uede. 2003. Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. J. Clin. Invest. 112: 181-188. https://doi.org/10.1172/JCI17778
  13. Weber, G. F., S. Ashkar, M. J. Glimcher, and H. Cantor. 1996. Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science 271: 509-512. https://doi.org/10.1126/science.271.5248.509
  14. Katagiri, Y. U., J. Sleeman, H. Fujii, P. Herrlich, H. Hotta, K. Tanaka, S. Chikuma, H. Yagita, K. Okumura, M. Murakami, I. Saiki, A. F. Chambers, and T. Uede. 1999. CD44 variants but not CD44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis. Cancer Res. 59: 219-226.
  15. Kanayama, M., D. Kurotaki, J. Morimoto, T. Asano, Y. Matsui, Y. Nakayama, Y. Saito, K. Ito, C. Kimura, N. Iwasaki, K. Suzuki, T. Harada, H. M. Li, J. Uehara, T. Miyazaki, A. Minami, S. Kon, and T. Uede. 2009. Alpha9 integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis. J. Immunol. 182: 8015-8025. https://doi.org/10.4049/jimmunol.0900725
  16. Morimoto, J., S Kon, Y. Matsui, and T. Uede. 2010. Osteopontin; as a target molecule for the treatment of inflammatory diseases. Curr. Drug Targets 11: 494-505. https://doi.org/10.2174/138945010790980321
  17. Diao, H., S. Kon, K. Iwabuchi, C. Kimura, J. Morimoto, D. Ito, T. Segawa, M. Maeda, J. Hamuro, T. Nakayama, M. Taniguchi, H. Yagita, L. K. Van Kaer, Onoe, D. Denhardt, S. Rittling, and T. Uede. 2004. Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases. Immunity 21: 539-550. https://doi.org/10.1016/j.immuni.2004.08.012
  18. Chung, J. W., M S. Kim, Z. H. Piao, M. Jeong, S. R. Yoon, N. Shin, S. Y. Kim, E. S. Hwang, Y. Yang, Y. H. Lee, Y. S. Kim, and I. Choi. 2008. Osteopontin promotes the development of natural killer cells from hematopoietic stem cells. Stem Cells 26: 2114-2123. https://doi.org/10.1634/stemcells.2008-0370
  19. Diao, H., K. Iwabuchi, L. Li, K. Onoe, L. Van Kaer, S. Kon, Y. Saito, J. Morimoto, D. T. Denhardt, S. Rittling, and T. Uede. 2008. Osteopontin regulates development and function of invariant natural killer T cells. Proc. Natl. Acad. Sci. U. S. A. 105: 15884-15889. https://doi.org/10.1073/pnas.0806089105
  20. Weber, C. E., N. Y. Li, P. Y. Wai, and P. C. Kuo. 2012. Epithelial-mesenchymal transition, TGF-$\beta$, and osteopontin in wound healing and tissue remodeling after injury. J. Burn. Care Res. 33: 311-318. https://doi.org/10.1097/BCR.0b013e318240541e
  21. Brown, L. F., B. Berse, L. Van de Water, A. Papadopoulos-Sergiou, C. A. Perruzzi, E. J. Manseau, H. F. Dvorak, and D. R. Senger. 1992. Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. Mol. Biol. Cell 3: 1169-1180. https://doi.org/10.1091/mbc.3.10.1169
  22. Ashizawa, N., K. Graf, Y. S. Do, T. Nunohiro, C. M. Giachelli, W. P. Meehan, T. L. Tuan, W. A. Hsueh. 1996. Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction. J. Clin. Invest. 98: 2218-2227. https://doi.org/10.1172/JCI119031
  23. Liaw. L., D. E. Birk, C. B. Ballas, J. S. Whitsitt, J. M. Davidson, and B. L. Hogan. 1998. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J. Clin. Invest. 101: 1468-1478. https://doi.org/10.1172/JCI2131
  24. Konno, S., M. Kurokawa, T. Uede, M. Nishimura, and S. K. Huang. 2011. Role of osteopontin, a multifunctional protein, in allergy and asthma. Clin. Exp. Allergy 41: 1360-1366. https://doi.org/10.1111/j.1365-2222.2011.03775.x
  25. Pardo, A., K. Gibson, J. Cisneros, T. J. Richards, Y. Yang, C. Becerril, S. Yousem, I. Herrera, V. Ruiz, M. Selman, and N. Kaminski. 2005. Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis. PLoS Med. 2: e251. https://doi.org/10.1371/journal.pmed.0020251
  26. Kelly, M. M., R. Leigh, S. E. Gilpin, E. Cheng, G. E. Martin, K. Radford, G. Cox, and J. Gauldie. 2006. Cell-specific gene expression in patients with usual interstitial pneumonia. Am. J. Respir. Crit. Care Med. 174: 557-565. https://doi.org/10.1164/rccm.200510-1648OC
  27. Takahashi, F., K. Takahashi, T. Okazaki, K. Maeda, H. Ienaga, M. Maeda, S. Kon, T. Uede, and Y. Fukuchi. 2001. Role of osteopontin in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 24: 264-271. https://doi.org/10.1165/ajrcmb.24.3.4293
  28. Berman, J. S., D. Serlin, X. Li, G. Whitley, J. Hayes, D.C. Rishikof, D. A. Ricupero, L. Liaw, M. Goetschkes, and A. W. O'Regan. 2004. Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L1311-1318. https://doi.org/10.1152/ajplung.00394.2003
  29. Shinohara, M. L., L. Lu, J. Bu, M. B. Werneck, K. S. Kobayashi, L. H. Glimcher, and H. Cantor. 2006. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat. Immunol. 7: 498-506. https://doi.org/10.1038/ni1327
  30. Cantor, H., and M. L. Shinohara. 2009. Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nat. Rev. Immunol. 9: 137-141. https://doi.org/10.1038/nri2460
  31. Baroni G. S., L. D'Ambrosio, P. Curto, A. Casini, R. Mancini, A. M. Jezequel, and A. Benedetti. 1996. Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology 23: 1189-1199. https://doi.org/10.1002/hep.510230538
  32. Giri, S. N., D. M. Hyde, and B. J. Marafino Jr. 1986. Ameliorating effect of murine interferon gamma on bleomycin-induced lung collagen fibrosis in mice. Biochem. Med. Metab. Biol. 36: 194-197. https://doi.org/10.1016/0885-4505(86)90124-6
  33. Oldroyd, S. D., G. L. Thomas, G. Gabbiani, and A. M. EI Nahas. 1996. Interferon-gamma inhibits experimental renal fibrosis. Kidney Int. 56: 2116-2127.
  34. Ashkar, S., G. F. Weber, V. Panoutsakopoulou, M. E. Sanchirico, M. Jansson, S. Zawaideh, S. R. Rittling, D. T. Denhardt, M. J. Glimcher, and H. Cantor. 2000. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287: 860-864. https://doi.org/10.1126/science.287.5454.860
  35. Murugaiyan, G., A. Mittal, and H. L. Weiner. 2010. Identification of an IL-27/osteopontin axis in dendritic cells and its modulation by IFN-gamma limits IL-17-mediated autoimmune inflammation. Proc. Natl. Acad. Sci. U. S. A. 107: 11495-11500. https://doi.org/10.1073/pnas.1002099107
  36. Shinohara, M. L., J. H. Kim, V. A. Garcia, and H. Cantor. 2008. Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 29: 68-78. https://doi.org/10.1016/j.immuni.2008.05.008
  37. Wynn, T. A., 2004. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat. Rev. Immunol. 4: 583-594. https://doi.org/10.1038/nri1412
  38. Braun, R. K., C. Ferrick, P. Neubauer, M. Sjoding, A. Sterner-Kock, M. Kock, L. Putney, D. A. Ferrick, D. M. Hyde, and R. B. Love. 2008. IL-17 producing gammadelta T cells are required for a controlled inflammatory response after bleomycin-induced lung injury. Inflammation 31: 167-179. https://doi.org/10.1007/s10753-008-9062-6
  39. Simonian, P. L., C. L. Roark, F. Diaz del Valle, B. E. Palmer, I. S. Douglas, K. Ikuta, W. K. Born, R. L. O'Brien, and A. P. Fontenot. 2006. Regulatory role of gammadelta T cells in the recruitment of $CD4^+$ and $CD8^+$ T cells to lung and subsequent pulmonary fibrosis. J. Immunol. 177: 4436-4443. https://doi.org/10.4049/jimmunol.177.7.4436
  40. Simonian, P. L., F. Wehrmann, C. L. Roark, W. K. Born, R. L. O'Brien, and A. P. Fontenot. 2010. ${\gamma}{\delta}T$ cells protect against lung fibrosis via IL-22. J. Exp. Med. 207: 2239-2253. https://doi.org/10.1084/jem.20100061

Cited by

  1. Role of Osteopontin in the Carcinogenesis and Metastasis of Colorectal Cancer vol.7, pp.10, 2015, https://doi.org/10.4236/jct.2016.710074
  2. Osteopontin—A Master Regulator of Epithelial-Mesenchymal Transition vol.5, pp.4, 2016, https://doi.org/10.3390/jcm5040039
  3. Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis vol.11, pp.12, 2015, https://doi.org/10.1371/journal.pone.0167435
  4. Matricellular Proteins and Organ Fibrosis vol.5, pp.2, 2015, https://doi.org/10.1007/s40139-017-0138-6
  5. Mediation of the single-walled carbon nanotubes induced pulmonary fibrogenic response by osteopontin and TGF-β1 vol.43, pp.8, 2015, https://doi.org/10.1080/01902148.2017.1377783
  6. Dihydroartemisinin alleviates oxidative stress in bleomycin-induced pulmonary fibrosis vol.205, pp.None, 2015, https://doi.org/10.1016/j.lfs.2018.05.022
  7. IL-17 in the lung: the good, the bad, and the ugly vol.314, pp.1, 2015, https://doi.org/10.1152/ajplung.00344.2017
  8. Osteopontin plays a pivotal role in increasing severity of respiratory syncytial virus infection vol.13, pp.4, 2015, https://doi.org/10.1371/journal.pone.0192709
  9. Dexamethasone reduces serum level of IL-17 in Bleomycin-A5-induced rats model of pulmonary fibrosis vol.46, pp.4, 2015, https://doi.org/10.1080/21691401.2017.1339051
  10. Association between osteopontin expression and asthma: a meta-analysis vol.47, pp.8, 2015, https://doi.org/10.1177/0300060519860684
  11. Emerging Roles of Matricellular Proteins in Systemic Sclerosis vol.21, pp.13, 2015, https://doi.org/10.3390/ijms21134776