Skip to main content
Erschienen in: Inflammation 3/2014

01.06.2014

IL-21 Is Increased in Peripheral Blood of Emphysema Mice and Promotes Th1/Tc1 Cell Generation In Vitro

verfasst von: Minchao Duan, Ying Huang, Xiaoning Zhong, Haijuan Tang

Erschienen in: Inflammation | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Interleukin-21 (IL-21) has been reported to be involved in many Th1-associated diseases. However, the alteration and immune regulation of IL-21 in emphysema remains unknown. In this study, we tested the levels of IFN-γ and IL-21 and the frequencies of Th1 and Tc1 in peripheral blood from cigarette smoke (CS)-exposed mice and air-exposed mice and explored the effect of IL-21 on generation of Th1 and Tc1 cells in vitro. It was found that the levels of IFN-γ and IL-21 and the frequencies of Th1, Tc1, CD4+ IL-21+, CD4+ IL-21R+, and CD8+ IL-21R+ T cells were much higher in CS-exposed mice. Moreover, the levels of IL-21 were correlated positively with Th1 cells and with Tc1 cells. Finally, the in vitro experiments showed that IL-21 could promote Th1/Tc1 cell generation in CS-exposed mice. These results indirectly provide evidence that IL-21 produced by CD4+ T cells could promote Th1/Tc1 response, leading to systemic inflammation in emphysema.
Literatur
1.
Zurück zum Zitat Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, et al. 2012 Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, GOLD executive summary. American Journal Respiratory Critical Care Medicine 9. Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, et al. 2012 Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, GOLD executive summary. American Journal Respiratory Critical Care Medicine 9.
2.
Zurück zum Zitat Murray, C.J., and A.D. Lopez. 1997. Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study. Lancet 349: 1498–1504.PubMedCrossRef Murray, C.J., and A.D. Lopez. 1997. Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study. Lancet 349: 1498–1504.PubMedCrossRef
3.
Zurück zum Zitat Barnes, P.J., S.D. Shapiro, and R.A. Pauwels. 2003. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. The European Respiratory Journal 22: 672–688.PubMedCrossRef Barnes, P.J., S.D. Shapiro, and R.A. Pauwels. 2003. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. The European Respiratory Journal 22: 672–688.PubMedCrossRef
4.
Zurück zum Zitat Barnes, P.J. 2008. Immunology of asthma and1 chronic obstructive pulmonary disease. Nature Reviews Immunology 8: 183–192.PubMedCrossRef Barnes, P.J. 2008. Immunology of asthma and1 chronic obstructive pulmonary disease. Nature Reviews Immunology 8: 183–192.PubMedCrossRef
5.
Zurück zum Zitat Sun, J.C., M.A. Williams, and M.J. Bevan. 2004. CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nature Immunology 5: 927–933.PubMedCentralPubMedCrossRef Sun, J.C., M.A. Williams, and M.J. Bevan. 2004. CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nature Immunology 5: 927–933.PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Cosio, M.G., and J. Majo. 2002. Inflammation of the airways and lung parenchyma in COPD: role of T cells. Chest 121: 160S–165S.PubMedCrossRef Cosio, M.G., and J. Majo. 2002. Inflammation of the airways and lung parenchyma in COPD: role of T cells. Chest 121: 160S–165S.PubMedCrossRef
8.
Zurück zum Zitat Grumelli, S., D.B. Corry, L.Z. Song, L. Song, L. Green, J. Huh, et al. 2004. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Medicine 1: e8.PubMedCentralPubMedCrossRef Grumelli, S., D.B. Corry, L.Z. Song, L. Song, L. Green, J. Huh, et al. 2004. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Medicine 1: e8.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Chrysofakis, G., N. Tzanakis, D. Kyriakoy, M. Tsoumakidou, I. Tsiligianni, M. Klimathianaki, et al. 2004. Perforin expression and cytotoxic activity of sputum CD8+ lymphocytes in patients with COPD. Chest 125: 71–76.PubMedCrossRef Chrysofakis, G., N. Tzanakis, D. Kyriakoy, M. Tsoumakidou, I. Tsiligianni, M. Klimathianaki, et al. 2004. Perforin expression and cytotoxic activity of sputum CD8+ lymphocytes in patients with COPD. Chest 125: 71–76.PubMedCrossRef
10.
11.
Zurück zum Zitat Debigaré, R., C.H. Côté, and F. Maltais. 2001. Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. American Journal of Respiratory and Critical Care Medicine 164: 1712–1717.PubMedCrossRef Debigaré, R., C.H. Côté, and F. Maltais. 2001. Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. American Journal of Respiratory and Critical Care Medicine 164: 1712–1717.PubMedCrossRef
12.
Zurück zum Zitat Fabbri, L.M., and K.F. Rabe. 2007. From COPD to chronic systemic inflammatory syndrome? Lancet 370: 797–799.PubMedCrossRef Fabbri, L.M., and K.F. Rabe. 2007. From COPD to chronic systemic inflammatory syndrome? Lancet 370: 797–799.PubMedCrossRef
14.
Zurück zum Zitat Parrish-Novak, J., S.R. Dillon, A. Nelson, A. Hammond, C. Sprecher, J.A. Gross, et al. 2000. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408: 57–63.PubMedCrossRef Parrish-Novak, J., S.R. Dillon, A. Nelson, A. Hammond, C. Sprecher, J.A. Gross, et al. 2000. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408: 57–63.PubMedCrossRef
15.
Zurück zum Zitat Mehta, D.S., A.L. Wurster, and M.J. Grusby. 2004. Biology of IL-21 and the IL-21 receptor. Immunology Reviews 202: 84–95.CrossRef Mehta, D.S., A.L. Wurster, and M.J. Grusby. 2004. Biology of IL-21 and the IL-21 receptor. Immunology Reviews 202: 84–95.CrossRef
16.
Zurück zum Zitat Monteleone, G., I. Monteleone, D. Fina, P. Vavassori, G. Del Vecchio Blanco, R. Caruso, et al. 2005. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Gastroenterology 128: 687–694.PubMedCrossRef Monteleone, G., I. Monteleone, D. Fina, P. Vavassori, G. Del Vecchio Blanco, R. Caruso, et al. 2005. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Gastroenterology 128: 687–694.PubMedCrossRef
17.
Zurück zum Zitat Pelletier, M., A. Bouchard, and D. Girard. 2004. In vivo and in vitro roles of IL-21 in inflammation. The Journal of Immunology 173: 7521–7530.PubMedCrossRef Pelletier, M., A. Bouchard, and D. Girard. 2004. In vivo and in vitro roles of IL-21 in inflammation. The Journal of Immunology 173: 7521–7530.PubMedCrossRef
18.
Zurück zum Zitat Herber, D., T.P. Brown, S. Liang, D.A. Young, M. Collins, and K. Dunussi-Joannopoulos. 2007. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. The Journal of Immunology 178: 3822–3830.PubMedCrossRef Herber, D., T.P. Brown, S. Liang, D.A. Young, M. Collins, and K. Dunussi-Joannopoulos. 2007. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. The Journal of Immunology 178: 3822–3830.PubMedCrossRef
19.
Zurück zum Zitat Stefanska, A.M., and P.T. Walsh. 2009. Chronic obstructive pulmonary disease: evidence for an autoimmune component. Cellular and Molecular Immunology 6: 81–86.PubMedCrossRef Stefanska, A.M., and P.T. Walsh. 2009. Chronic obstructive pulmonary disease: evidence for an autoimmune component. Cellular and Molecular Immunology 6: 81–86.PubMedCrossRef
20.
Zurück zum Zitat Vollmer, T.L., R. Liu, M. Price, S. Rhodes, A. La Cava, and F.D. Shi. 2005. Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen. The Journal of Immunology 174: 2696–2701.PubMedCrossRef Vollmer, T.L., R. Liu, M. Price, S. Rhodes, A. La Cava, and F.D. Shi. 2005. Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen. The Journal of Immunology 174: 2696–2701.PubMedCrossRef
21.
Zurück zum Zitat Huang, Y., X.N. Zhong, M.C. Duan, and H.J. Tang. 2012. Expression of interleukin-21 in the lungs of mice with emphysema and its effects on the differentiation of CD4+ T cell. Zhonghua Yi Xue Za Zhi 92: 1129–1132.PubMed Huang, Y., X.N. Zhong, M.C. Duan, and H.J. Tang. 2012. Expression of interleukin-21 in the lungs of mice with emphysema and its effects on the differentiation of CD4+ T cell. Zhonghua Yi Xue Za Zhi 92: 1129–1132.PubMed
22.
Zurück zum Zitat D'hulst, A.I., K.Y. Vermaelen, G.G. Brusselle, G.F. Joos, and R.A. Pauwels. 2005. Time course of cigarette smoke-induced pulmonary inflammation in mice. The European Respiratory Journal 26: 204–213.PubMedCrossRef D'hulst, A.I., K.Y. Vermaelen, G.G. Brusselle, G.F. Joos, and R.A. Pauwels. 2005. Time course of cigarette smoke-induced pulmonary inflammation in mice. The European Respiratory Journal 26: 204–213.PubMedCrossRef
23.
Zurück zum Zitat Macdonald, G., N. Kondor, V. Yousefi, A. Green, F. Wong, and C. Aquino-Parsons. 2004. Reduction of carboxyhaemoglobin levels in the venous blood of cigarette smokers following the administration of carbogen. Radiotherapy and Oncology 73: 367–371.PubMedCrossRef Macdonald, G., N. Kondor, V. Yousefi, A. Green, F. Wong, and C. Aquino-Parsons. 2004. Reduction of carboxyhaemoglobin levels in the venous blood of cigarette smokers following the administration of carbogen. Radiotherapy and Oncology 73: 367–371.PubMedCrossRef
24.
Zurück zum Zitat Thurlbeck, W.M. 1967. Measurement of pulmonary emphysema. The American Review of Respiratory Disease 95: 752–764.PubMed Thurlbeck, W.M. 1967. Measurement of pulmonary emphysema. The American Review of Respiratory Disease 95: 752–764.PubMed
25.
Zurück zum Zitat Vosshenrich, C.A., and J.P. Di Santo. 2001. Cytokines: IL-21 joins the gamma(c)-dependent network? Current Biology 11: R175–R177.PubMedCrossRef Vosshenrich, C.A., and J.P. Di Santo. 2001. Cytokines: IL-21 joins the gamma(c)-dependent network? Current Biology 11: R175–R177.PubMedCrossRef
26.
Zurück zum Zitat Sarra, M., R. Caruso, M.L. Cupi, I. Monteleone, C. Stolfi, E. Campione, et al. 2011. IL-21 promotes skin recruitment of CD4(+) cells and drives IFN-γ-dependent epidermal hyperplasia. The Journal of Immunology 186: 5435–5442.PubMedCrossRef Sarra, M., R. Caruso, M.L. Cupi, I. Monteleone, C. Stolfi, E. Campione, et al. 2011. IL-21 promotes skin recruitment of CD4(+) cells and drives IFN-γ-dependent epidermal hyperplasia. The Journal of Immunology 186: 5435–5442.PubMedCrossRef
27.
Zurück zum Zitat Strengell, M., S. Matikainen, J. Sirén, A. Lehtonen, D. Foster, I. Julkunen, et al. 2003. IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells. The Journal of Immunology 170: 5464–5469.PubMedCrossRef Strengell, M., S. Matikainen, J. Sirén, A. Lehtonen, D. Foster, I. Julkunen, et al. 2003. IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells. The Journal of Immunology 170: 5464–5469.PubMedCrossRef
28.
Zurück zum Zitat Spolski, R., and W.J. Leonard. 2008. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annual Review of Immunology 26: 57–79.PubMedCrossRef Spolski, R., and W.J. Leonard. 2008. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annual Review of Immunology 26: 57–79.PubMedCrossRef
29.
Zurück zum Zitat Duan, M.C., X.N. Zhong, Y. Huang, Z.Y. He, and H.J. Tang. 2011. Effect of interleukin-17-producing CD4+ T helper lymphocytes on cigarette smoke-induced lung inflammation and emphysema in mice. Zhonghua Yi Xue Za Zhi 34: 259–264. Duan, M.C., X.N. Zhong, Y. Huang, Z.Y. He, and H.J. Tang. 2011. Effect of interleukin-17-producing CD4+ T helper lymphocytes on cigarette smoke-induced lung inflammation and emphysema in mice. Zhonghua Yi Xue Za Zhi 34: 259–264.
30.
Zurück zum Zitat Shirai, T., T. Suda, N. Inui, and K. Chida. 2010. Correlation between peripheral blood T-cell profiles and clinical and inflammatory parameters instable COPD. Allergology International 59: 75–82.PubMedCrossRef Shirai, T., T. Suda, N. Inui, and K. Chida. 2010. Correlation between peripheral blood T-cell profiles and clinical and inflammatory parameters instable COPD. Allergology International 59: 75–82.PubMedCrossRef
31.
Zurück zum Zitat Ozaki, K., K. Kikly, D. Michalovich, P.R. Young, and W.J. Leonard. 2000. Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proceedings of the National Academy of Sciences of the United States of America 97: 11439–11444.PubMedCentralPubMedCrossRef Ozaki, K., K. Kikly, D. Michalovich, P.R. Young, and W.J. Leonard. 2000. Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proceedings of the National Academy of Sciences of the United States of America 97: 11439–11444.PubMedCentralPubMedCrossRef
32.
Zurück zum Zitat Jin, H., R. Carrio, A. Yu, and T.R. Malek. 2004. Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. The Journal of Immunology 173: 657–665.PubMedCrossRef Jin, H., R. Carrio, A. Yu, and T.R. Malek. 2004. Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. The Journal of Immunology 173: 657–665.PubMedCrossRef
33.
Zurück zum Zitat Brandt, K., S. Bulfone-Paus, D.C. Foster, and R. Ruckert. 2003. Interleukin-21 inhibits dendritic cell activation and maturation. Blood 102: 4090–4098.PubMedCrossRef Brandt, K., S. Bulfone-Paus, D.C. Foster, and R. Ruckert. 2003. Interleukin-21 inhibits dendritic cell activation and maturation. Blood 102: 4090–4098.PubMedCrossRef
34.
Zurück zum Zitat Duan MC, Huang Y, Zhong XN, Tang HJ 2012 Th17 cell enhances CD8 T-cell cytotoxicity via IL-21 production in emphysema mice. Mediators Inflammation. Epub 2012 Dec 25. Duan MC, Huang Y, Zhong XN, Tang HJ 2012 Th17 cell enhances CD8 T-cell cytotoxicity via IL-21 production in emphysema mice. Mediators Inflammation. Epub 2012 Dec 25.
35.
Zurück zum Zitat Zhang, J., S. Chu, X. Zhong, Q. Lao, Z. He, and Y. Liang. 2013. Increased expression of CD4 + IL-17+ cells in the lung tissue of patients with stable chronic obstructive pulmonary disease (COPD) and Smokers. International Immunopharmacology 15: 58–66.PubMedCrossRef Zhang, J., S. Chu, X. Zhong, Q. Lao, Z. He, and Y. Liang. 2013. Increased expression of CD4 + IL-17+ cells in the lung tissue of patients with stable chronic obstructive pulmonary disease (COPD) and Smokers. International Immunopharmacology 15: 58–66.PubMedCrossRef
36.
Zurück zum Zitat Di Stefano, A., G. Caramori, I. Gnemmi, M. Contoli, C. Vicari, A. Capelli, et al. 2009. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clinical and Experimental Immunology 157: 316–324.PubMedCentralPubMedCrossRef Di Stefano, A., G. Caramori, I. Gnemmi, M. Contoli, C. Vicari, A. Capelli, et al. 2009. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clinical and Experimental Immunology 157: 316–324.PubMedCentralPubMedCrossRef
37.
Zurück zum Zitat Strengell, M., T. Sareneva, D. Foster, I. Julkunen, and S. Matikainen. 2002. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. The Journal of Immunology 169: 3600–3605.PubMedCrossRef Strengell, M., T. Sareneva, D. Foster, I. Julkunen, and S. Matikainen. 2002. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. The Journal of Immunology 169: 3600–3605.PubMedCrossRef
38.
Zurück zum Zitat Kasaian, M.T., M.J. Whitters, L.L. Carter, L.D. Lowe, J.M. Jussif, B. Deng, et al. 2002. IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity 16: 559–569.PubMedCrossRef Kasaian, M.T., M.J. Whitters, L.L. Carter, L.D. Lowe, J.M. Jussif, B. Deng, et al. 2002. IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity 16: 559–569.PubMedCrossRef
39.
Zurück zum Zitat Wurster, A.L., V.L. Rodgers, A.R. Satoskar, M.J. Whitters, D.A. Young, M. Collins, et al. 2002. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells. The Journal of Experimental Medicine 196: 969–977.PubMedCentralPubMedCrossRef Wurster, A.L., V.L. Rodgers, A.R. Satoskar, M.J. Whitters, D.A. Young, M. Collins, et al. 2002. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells. The Journal of Experimental Medicine 196: 969–977.PubMedCentralPubMedCrossRef
40.
Zurück zum Zitat Suto, A., A.L. Wurster, S.L. Reiner, and M.J. Grusby. 2006. IL-21 inhibits IFN-γ production in developing Th1 cells through the repression of Eomesodermin expression. The Journal of Immunology 177: 3721–3727.PubMedCrossRef Suto, A., A.L. Wurster, S.L. Reiner, and M.J. Grusby. 2006. IL-21 inhibits IFN-γ production in developing Th1 cells through the repression of Eomesodermin expression. The Journal of Immunology 177: 3721–3727.PubMedCrossRef
Metadaten
Titel
IL-21 Is Increased in Peripheral Blood of Emphysema Mice and Promotes Th1/Tc1 Cell Generation In Vitro
verfasst von
Minchao Duan
Ying Huang
Xiaoning Zhong
Haijuan Tang
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 3/2014
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-013-9793-x

Weitere Artikel der Ausgabe 3/2014

Inflammation 3/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.