請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/4763完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 江伯倫(Bor-Luen Chiang) | |
| dc.contributor.author | Chiao-Juno Chiu | en |
| dc.contributor.author | 邱巧絨 | zh_TW |
| dc.date.accessioned | 2021-05-14T17:46:42Z | - |
| dc.date.available | 2015-09-24 | |
| dc.date.available | 2021-05-14T17:46:42Z | - |
| dc.date.copyright | 2015-09-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-03-26 | |
| dc.identifier.citation | 1. Busse WW, Lemanske RF, Jr. Asthma. N Engl J Med 2001; 344:350-62.
2. Grainge CL, Davies DE. Epithelial injury and repair in airways diseases. Chest 2013; 144:1906-12. 3. Bousquet J, Kaltaev N. Global surveillance, prevention and control of chronic respiratory diseases : a comprehensive approach. Geneva: World Health Organization; 2007. 4. Dahl R. Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med 2006; 100:1307-17. 5. Sueblinvong V, Weiss DJ. Stem cells and cell therapy approaches in lung biology and diseases. Transl Res 2010; 156:188-205. 6. Kim HY, DeKruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol 2010; 11:577-84. 7. Johnston RA, Zhu M, Rivera-Sanchez YM, Lu FL, Theman TA, Flynt L, et al. Allergic airway responses in obese mice. Am J Respir Crit Care Med 2007; 176:650-8. 8. Pichavant M, Goya S, Meyer EH, Johnston RA, Kim HY, Matangkasombut P, et al. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J Exp Med 2008; 205:385-93. 9. Kim EY, Battaile JT, Patel AC, You Y, Agapov E, Grayson MH, et al. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med 2008; 14:633-40. 10. Wamboldt MZ, Laudenslager M, Wamboldt FS, Kelsay K, Hewitt J. Adolescents with atopic disorders have an attenuated cortisol response to laboratory stress. J Allergy Clin Immunol 2003; 111:509-14. 11. Larche M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 2006; 6:761-71. 12. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. Role of Treg in immune regulation of allergic diseases. Eur J Immunol 2010; 40:1232-40. 13. Lloyd CM, Hessel EM. Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol 2010; 10:838-48. 14. Gould HJ, Sutton BJ. IgE in allergy and asthma today. Nat Rev Immunol 2008; 8:205-17. 15. Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol 2010; 10:225-35. 16. Takatsu K, Nakajima H. IL-5 and eosinophilia. Curr Opin Immunol 2008; 20:288-94. 17. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 2013; 13:9-22. 18. Ingram JL, Kraft M. IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies. J Allergy Clin Immunol 2012; 130:829-42; quiz 43-4. 19. Wills-Karp M. Interleukin-13 in asthma pathogenesis. Immunol Rev 2004; 202:175-90. 20. Cohn L, Homer RJ, Marinov A, Rankin J, Bottomly K. Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production. J Exp Med 1997; 186:1737-47. 21. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008; 322:271-5. 22. Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 2004; 199:1567-75. 23. Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, et al. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity 2008; 29:771-81. 24. Ring S, Schafer SC, Mahnke K, Lehr HA, Enk AH. CD4+ CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue. Eur J Immunol 2006; 36:2981-92. 25. Joetham A, Takeda K, Taube C, Miyahara N, Matsubara S, Koya T, et al. Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta. J Immunol 2007; 178:1433-42. 26. Kearley J, Barker JE, Robinson DS, Lloyd CM. Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med 2005; 202:1539-47. 27. Ostroukhova M, Seguin-Devaux C, Oriss TB, Dixon-McCarthy B, Yang L, Ameredes BT, et al. Tolerance induced by inhaled antigen involves CD4(+) T cells expressing membrane-bound TGF-beta and FOXP3. J Clin Invest 2004; 114:28-38. 28. Strickland DH, Stumbles PA, Zosky GR, Subrata LS, Thomas JA, Turner DJ, et al. Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. J Exp Med 2006; 203:2649-60. 29. Nguyen KD, Vanichsarn C, Fohner A, Nadeau KC. Selective deregulation in chemokine signaling pathways of CD4+CD25(hi)CD127(lo)/(-) regulatory T cells in human allergic asthma. J Allergy Clin Immunol 2009; 123:933-9 e10. 30. Hartl D, Koller B, Mehlhorn AT, Reinhardt D, Nicolai T, Schendel DJ, et al. Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma. J Allergy Clin Immunol 2007; 119:1258-66. 31. Fulkerson PC, Rothenberg ME. Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov 2013; 12:117-29. 32. Brottman GM, Regelmann WE, Slungaard A, Wangensteen OD. Effect of eosinophil peroxidase on airway epithelial permeability in the guinea pig. Pediatr Pulmonol 1996; 21:159-66. 33. Gleich GJ, Frigas E, Loegering DA, Wassom DL, Steinmuller D. Cytotoxic properties of the eosinophil major basic protein. J Immunol 1979; 123:2925-7. 34. Kampen GT, Stafford S, Adachi T, Jinquan T, Quan S, Grant JA, et al. Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases. Blood 2000; 95:1911-7. 35. Tenscher K, Metzner B, Schopf E, Norgauer J, Czech W. Recombinant human eotaxin induces oxygen radical production, Ca(2+)-mobilization, actin reorganization, and CD11b upregulation in human eosinophils via a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding protein. Blood 1996; 88:3195-9. 36. Ying S, Robinson DS, Meng Q, Rottman J, Kennedy R, Ringler DJ, et al. Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur J Immunol 1997; 27:3507-16. 37. Schuh JM, Blease K, Kunkel SL, Hogaboam CM. Eotaxin/CCL11 is involved in acute, but not chronic, allergic airway responses to Aspergillus fumigatus. Am J Physiol Lung Cell Mol Physiol 2002; 283:L198-204. 38. Pope SM, Zimmermann N, Stringer KF, Karow ML, Rothenberg ME. The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. J Immunol 2005; 175:5341-50. 39. Ma W, Bryce PJ, Humbles AA, Laouini D, Yalcindag A, Alenius H, et al. CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest 2002; 109:621-8. 40. Fulkerson PC, Fischetti CA, McBride ML, Hassman LM, Hogan SP, Rothenberg ME. A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proc Natl Acad Sci U S A 2006; 103:16418-23. 41. Kim J, Merry AC, Nemzek JA, Bolgos GL, Siddiqui J, Remick DG. Eotaxin represents the principal eosinophil chemoattractant in a novel murine asthma model induced by house dust containing cockroach allergens. J Immunol 2001; 167:2808-15. 42. Lambrecht BN, Hammad H. The airway epithelium in asthma. Nat Med 2012; 18:684-92. 43. Hammad H, Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol 2008; 8:193-204. 44. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 2009; 15:410-6. 45. Willart MA, Deswarte K, Pouliot P, Braun H, Beyaert R, Lambrecht BN, et al. Interleukin-1alpha controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33. J Exp Med 2012; 209:1505-17. 46. Licona-Limon P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 2013; 14:536-42. 47. Saenz SA, Taylor BC, Artis D. Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites. Immunol Rev 2008; 226:172-90. 48. Semlali A, Jacques E, Koussih L, Gounni AS, Chakir J. Thymic stromal lymphopoietin-induced human asthmatic airway epithelial cell proliferation through an IL-13-dependent pathway. J Allergy Clin Immunol 2010; 125:844-50. 49. Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, et al. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med 2005; 202:1213-23. 50. Zhou B, Comeau MR, De Smedt T, Liggitt HD, Dahl ME, Lewis DB, et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol 2005; 6:1047-53. 51. He R, Oyoshi MK, Garibyan L, Kumar L, Ziegler SF, Geha RS. TSLP acts on infiltrating effector T cells to drive allergic skin inflammation. Proc Natl Acad Sci U S A 2008; 105:11875-80. 52. Boehme SA, Franz-Bacon K, Chen EP, Sasik R, Sprague LJ, Ly TW, et al. A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. Int Immunol 2009; 21:81-93. 53. Al-Shami A, Spolski R, Kelly J, Keane-Myers A, Leonard WJ. A role for TSLP in the development of inflammation in an asthma model. J Exp Med 2005; 202:829-39. 54. Asquith KL, Ramshaw HS, Hansbro PM, Beagley KW, Lopez AF, Foster PS. The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. J Immunol 2008; 180:1199-206. 55. Stampfli MR, Wiley RE, Neigh GS, Gajewska BU, Lei XF, Snider DP, et al. GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice. J Clin Invest 1998; 102:1704-14. 56. Cates EC, Fattouh R, Wattie J, Inman MD, Goncharova S, Coyle AJ, et al. Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism. J Immunol 2004; 173:6384-92. 57. Bleck B, Tse DB, Jaspers I, Curotto de Lafaille MA, Reibman J. Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation. J Immunol 2006; 176:7431-7. 58. Ohta K, Yamashita N, Tajima M, Miyasaka T, Nakano J, Nakajima M, et al. Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF. J Allergy Clin Immunol 1999; 104:1024-30. 59. Schmitz N, Kurrer M, Kopf M. The IL-1 receptor 1 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model. Eur J Immunol 2003; 33:991-1000. 60. Eiwegger T, Akdis CA. IL-33 links tissue cells, dendritic cells and Th2 cell development in a mouse model of asthma. Eur J Immunol 2011; 41:1535-8. 61. Kurowska-Stolarska M, Stolarski B, Kewin P, Murphy G, Corrigan CJ, Ying S, et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol 2009; 183:6469-77. 62. Chu DK, Llop-Guevara A, Walker TD, Flader K, Goncharova S, Boudreau JE, et al. IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization. J Allergy Clin Immunol 2013; 131:187-200 e1-8. 63. Lambrecht BN, De Veerman M, Coyle AJ, Gutierrez-Ramos JC, Thielemans K, Pauwels RA. Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest 2000; 106:551-9. 64. Wills-Karp M, Rani R, Dienger K, Lewkowich I, Fox JG, Perkins C, et al. Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection. J Exp Med 2012; 209:607-22. 65. Petersen BC, Budelsky AL, Baptist AP, Schaller MA, Lukacs NW. Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology. Nat Med 2012; 18:751-8. 66. Gregory LG, Jones CP, Walker SA, Sawant D, Gowers KH, Campbell GA, et al. IL-25 drives remodelling in allergic airways disease induced by house dust mite. Thorax 2013; 68:82-90. 67. Herriges M, Morrisey EE. Lung development: orchestrating the generation and regeneration of a complex organ. Development 2014; 141:502-13. 68. Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, et al. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell 2014; 15:123-38. 69. Rawlins EL, Clark CP, Xue Y, Hogan BL. The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development 2009; 136:3741-5. 70. McQualter JL, Yuen K, Williams B, Bertoncello I. Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung. Proc Natl Acad Sci U S A 2010; 107:1414-9. 71. Rawlins EL. Lung epithelial progenitor cells: lessons from development. Proc Am Thorac Soc 2008; 5:675-81. 72. Kotton DN, Morrisey EE. Lung regeneration: mechanisms, applications and emerging stem cell populations. Nat Med 2014; 20:822-32. 73. Paul MK, Bisht B, Darmawan DO, Chiou R, Ha VL, Wallace WD, et al. Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling. Cell Stem Cell 2014; 15:199-214. 74. Rock JR, Onaitis MW, Rawlins EL, Lu Y, Clark CP, Xue Y, et al. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A 2009; 106:12771-5. 75. Tata PR, Mou H, Pardo-Saganta A, Zhao R, Prabhu M, Law BM, et al. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature 2013; 503:218-23. 76. Wansleeben C, Bowie E, Hotten DF, Yu YR, Hogan BL. Age-related changes in the cellular composition and epithelial organization of the mouse trachea. PLoS One 2014; 9:e93496. 77. Rock JR, Gao X, Xue Y, Randell SH, Kong YY, Hogan BL. Notch-dependent differentiation of adult airway basal stem cells. Cell Stem Cell 2011; 8:639-48. 78. Chen G, Korfhagen TR, Xu Y, Kitzmiller J, Wert SE, Maeda Y, et al. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. J Clin Invest 2009; 119:2914-24. 79. Barkauskas CE, Cronce MJ, Rackley CR, Bowie EJ, Keene DR, Stripp BR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest 2013; 123:3025-36. 80. Xu X, Rock JR, Lu Y, Futtner C, Schwab B, Guinney J, et al. Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma. Proc Natl Acad Sci U S A 2012; 109:4910-5. 81. Desai TJ, Brownfield DG, Krasnow MA. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature 2014; 507:190-4. 82. Reynolds SD, Reynolds PR, Pryhuber GS, Finder JD, Stripp BR. Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse and human airways. Am J Respir Crit Care Med 2002; 166:1498-509. 83. Giangreco A, Reynolds SD, Stripp BR. Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol 2002; 161:173-82. 84. Reynolds SD, Hong KU, Giangreco A, Mango GW, Guron C, Morimoto Y, et al. Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol 2000; 278:L1256-63. 85. Rawlins EL, Okubo T, Xue Y, Brass DM, Auten RL, Hasegawa H, et al. The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 2009; 4:525-34. 86. Johansson S, Wennergren G, Aberg N, Rudin A. Clara cell 16-kd protein downregulates T(H)2 differentiation of human naive neonatal T cells. J Allergy Clin Immunol 2007; 120:308-14. 87. Mandal AK, Zhang Z, Ray R, Choi MS, Chowdhury B, Pattabiraman N, et al. Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions. J Exp Med 2004; 199:1317-30. 88. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005; 121:823-35. 89. Lee JH, Bhang DH, Beede A, Huang TL, Stripp BR, Bloch KD, et al. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 2014; 156:440-55. 90. Bousquet J, Bachert C, Canonica GW, Casale TB, Cruz AA, Lockey RJ, et al. Unmet needs in severe chronic upper airway disease (SCUAD). J Allergy Clin Immunol 2009; 124:428-33. 91. Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 2001; 17:387-403. 92. Li L, Clevers H. Coexistence of quiescent and active adult stem cells in mammals. Science 2010; 327:542-5. 93. Ling TY, Kuo MD, Li CL, Yu AL, Huang YH, Wu TJ, et al. Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proc Natl Acad Sci U S A 2006; 103:9530-5. 94. van Rijt LS, Kuipers H, Vos N, Hijdra D, Hoogsteden HC, Lambrecht BN. A rapid flow cytometric method for determining the cellular composition of bronchoalveolar lavage fluid cells in mouse models of asthma. J Immunol Methods 2004; 288:111-21. 95. Barker N, Bartfeld S, Clevers H. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell 2010; 7:656-70. 96. Look DC, Walter MJ, Williamson MR, Pang L, You Y, Sreshta JN, et al. Effects of paramyxoviral infection on airway epithelial cell Foxj1 expression, ciliogenesis, and mucociliary function. Am J Pathol 2001; 159:2055-69. 97. You Y, Richer EJ, Huang T, Brody SL. Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population. Am J Physiol Lung Cell Mol Physiol 2002; 283:L1315-21. 98. Pinkerton KE, Joad JP. Influence of air pollution on respiratory health during perinatal development. Clin Exp Pharmacol Physiol 2006; 33:269-72. 99. Kajstura J, Rota M, Hall SR, Hosoda T, D'Amario D, Sanada F, et al. Evidence for human lung stem cells. N Engl J Med 2011; 364:1795-806. 100. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 2008; 118:3546-56. 101. Shijubo N, Itoh Y, Yamaguchi T, Sugaya F, Hirasawa M, Yamada T, et al. Serum levels of Clara cell 10-kDa protein are decreased in patients with asthma. Lung 1999; 177:45-52. 102. Van Vyve T, Chanez P, Bernard A, Bousquet J, Godard P, Lauwerijs R, et al. Protein content in bronchoalveolar lavage fluid of patients with asthma and control subjects. J Allergy Clin Immunol 1995; 95:60-8. 103. Cohen L, E X, Tarsi J, Ramkumar T, Horiuchi TK, Cochran R, et al. Epithelial cell proliferation contributes to airway remodeling in severe asthma. Am J Respir Crit Care Med 2007; 176:138-45. 104. Trifilieff A, El-Hashim A, Bertrand C. Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment. Am J Physiol Lung Cell Mol Physiol 2000; 279:L1120-8. 105. Kavanagh H, Mahon BP. Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy 2011; 66:523-31. 106. Goodwin M, Sueblinvong V, Eisenhauer P, Ziats NP, LeClair L, Poynter ME, et al. Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice. Stem Cells 2011; 29:1137-48. 107. Nemeth K, Keane-Myers A, Brown JM, Metcalfe DD, Gorham JD, Bundoc VG, et al. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci U S A 2010; 107:5652-7. 108. Walker N, Badri L, Wettlaufer S, Flint A, Sajjan U, Krebsbach PH, et al. Resident tissue-specific mesenchymal progenitor cells contribute to fibrogenesis in human lung allografts. Am J Pathol 2011; 178:2461-9. 109. Popova AP, Bozyk PD, Bentley JK, Linn MJ, Goldsmith AM, Schumacher RE, et al. Isolation of tracheal aspirate mesenchymal stromal cells predicts bronchopulmonary dysplasia. Pediatrics 2010; 126:e1127-33. 110. Holgate ST. Epithelium dysfunction in asthma. J Allergy Clin Immunol 2007; 120:1233-44; quiz 45-6. 111. Xu W, Lan Q, Chen M, Chen H, Zhu N, Zhou X, et al. Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation. PLoS One 2012; 7:e40314. 112. Burchell JT, Wikstrom ME, Stumbles PA, Sly PD, Turner DJ. Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells. Am J Physiol Lung Cell Mol Physiol 2009; 296:L307-19. 113. Jain-Vora S, Wert SE, Temann UA, Rankin JA, Whitsett JA. Interleukin-4 alters epithelial cell differentiation and surfactant homeostasis in the postnatal mouse lung. Am J Respir Cell Mol Biol 1997; 17:541-51. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/4763 | - |
| dc.description.abstract | 氣喘主要的症狀為慢性呼吸道發炎與呼吸道收縮阻力（airway hyperresponsiveness, AHR）增加。目前尚無探討肺部幹細胞/前驅幹細胞（pulmonary stem/progenitor cells, PSCs）與調控過敏性呼吸道發炎的相關研究。為了尋找並進一步研究PSCs，我們利用特殊的酵素分解法，由新生小鼠肺組織中分離出單一細胞懸浮液。利用流式細胞儀、即時聚合酶連鎖反應、免疫螢光染色、共軛焦顯微鏡及掃描式電子顯微鏡鑑定PSCs的特性。在體外細胞培養模式中，以流式細胞儀、酵素連結免疫吸附法、即時聚合酶連鎖反應及免疫轉漬法，分析PSCs的細胞調控機制；同時也探討PSCs對卵白蛋白引發過敏性呼吸道發炎動物模式的影響。結果發現，由新生鼠肺部組織所分離的單一細胞懸浮液，分別表現階段特異性胚胎抗原-1（stage-specific embryonic antigen-1, SSEA-1）或幹細胞抗原-1（stem cell antigen-1, Sca-1）。SSEA-1+ PSCs大量表現於新生鼠，但成鼠中則非常稀少。進一步純化後的SSEA-1+ PSCs可分化為肺細胞（penumocytes）與氣管上皮細胞（tracheal epithelial cells）。此外，與SSEA-1- 肺部細胞相較，SSEA-1+ PSCs表現高量的克拉拉細胞分泌蛋白（Clara cell secretory protein, CCSP）。移植SSEA-1+ PSCs至過敏性呼吸道發炎小鼠體內，可降低嗜酸性白血球（eosinophils）浸潤、抑制細胞趨化素/細胞激素、增加調節型T細胞（regulatory T cells）及維持肺部CCSP表現，進而達到減少呼吸道收縮阻力與肺部受損情形。本研究發現新生鼠之SSEA-1+ PSCs可降低肺部傷害與抑制發炎反應，進而對於氣喘進程具有免疫調節能力。深入了解SSEA-1+ PSCs免疫調控能力的分子機制將有助於開發未來治療呼吸道發炎的新策略。 | zh_TW |
| dc.description.abstract | Asthma is characterized by chronic airway inflammation and hyperresponsiveness (AHR). Little is known about the role of pulmonary stem cells (PSCs) in allergic airway inflammation. To identify the role of PSCs population in the bronchial epithelium of neonatal mice, we developed an enzyme-based digestion method to isolate PSCs from lung tissues. Characterization of PSCs was done using flow cytometry, real-time PCR, immunofluorescence staining, confocal microscopy, and scanning electron microscopy. The effects of SSEA-1+ PSCs was studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of cell-based regulation using flow cytometry, enzyme-linked immunosorbent assay, real-time PCR, and immune-blotting. Cell suspensions derived from neonatal lung tissue contained cells expressing either SSEA-1+ (stage-specific embryonic antigen-1) or Sca-1+ (stem cell antigen-1) that represent PSCs phenotype. The SSEA-1+ PSCs were prevalent in neonatal mice, but rare in adult mice. Enriched SSEA-1+ PSCs had the ability to differentiate into pneumocytes and tracheal epithelial cells. The expression of CCSP (Clara cell secretory protein) were higher in SSEA-1+ PSCs as compared with that of SSEA-1- pulmonary cells. Transplantation of SSEA-1+ PSCs in asthmatic mice reduced AHR and airway damage by decreasing eosinophil infiltration, inhibiting chemokines/cytokines production, increasing regulatory T cells, and preserving the level of CCSP. Collectively, our results indicated that neonatal SSEA-1+ PSCs contribute to ameliorate the progression of asthma by reducing lung damage and inhibiting inflammatory responses. Study about the molecular mechanisms of neonatal SSEA-1+ PSCs might shed light on etiology of airway inflammation. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-14T17:46:42Z (GMT). No. of bitstreams: 1 ntu-104-D96449004-1.pdf: 11481592 bytes, checksum: 3f15b6fe788522e6e5c2748ae42c065c (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | ABSTRACT…………………...………………………………………………… I
ABSTRACT IN CHINESE …………………………………………………. II ABBREVIATIONS……………………………………………………….……. III CONTENTS ……………………………………………………….………… IV CONTENTS OF FIGURES…………………………………………………….. VI I. INTRODUCTION……………………………………………………………. 1 1.1 Pathogenesis of asthma…………………………………………………….. 2 1.2 Regulatory T cells in asthma………………………………………………… 4 1.3 Eosinophils in allergic inflammation……………………………………….. 4 1.4 Airway epithelium is involved in the pathogenesis of asthma……………… 5 1.5 Cytokines secreted at the barrier that control TH2 immunity to allergens….. 6 1.6 Lung development………………………………………………………….. 8 1.7 Lung stem cells……………………………………………………………… 8 1.7.1 Basal cells. ……………………………………………………………….. 9 1.7.2 Type II pneumocytes……………………………………………………… 9 1.7.3 Club cells…………………………………………………………………. 10 1.7.4 Bronchioalveolar stem cells (BASCs) ……………………………………. 10 1.8 Lung stem cells and airway diseases………………………………………... 11 II. MATERIALS AND METHODS ………………………………………… 13 III. RESULTS…………………………………………………………………… 21 3.1 Identification of potential stem/progenitor cells from neonatal mouse lungs.. 22 3.2 Phenotypic characteristics of neonatal SSEA-1+ pulmonary cells………….. 23 3.3 Neonatal lung SSEA-1+ cells possess self-renewal, clonogenicity, and multipotency ability……………………………………………………………. 24 3.4 SSEA-1+ PSCs reduce TSLP and eotaxin production…………………….. 25 3.5 Transplantation of SSEA-1+ PSCs alleviates the severity of asthmatic features…………………….…………………….…………………….……….. 26 3.6 Transplantation of SSEA-1+ PSCs increase Foxp3+ Treg population……… 27 3.7 Transplantation of SSEA-1+ PSCs preserves the epithelium and inhibits unregulated lung structural cell proliferation in asthma………………………… 27 IV. DISCUSSION………………………………………………………………. 29 V. CONCLUSION AND PROSPECTS………………………………………… 35 VI. FIGURES……………………………………………………………………. 37 VII. REFFERENCES…………………………………………………………… 59 VIII. APPENDIX……………………………………………………………….. 74 | |
| dc.language.iso | en | |
| dc.subject | 氣喘 | zh_TW |
| dc.subject | 肺部幹細胞/前驅幹細胞 | zh_TW |
| dc.subject | 呼吸道發炎 | zh_TW |
| dc.subject | asthma | en |
| dc.subject | airway inflammation | en |
| dc.subject | Pulmonary stem/progenitor cell | en |
| dc.title | 分離與鑑定SSEA-1+肺部前驅幹細胞治療過敏性氣喘 | zh_TW |
| dc.title | Isolation and Characterization of SSEA-1+ Pulmonary Stem/Progenitor Cells for Treatment of Allergic Asthma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 賴明宗(Ming-Zong Lai),楊倍昌(Bei-Chang Yang),許秉寧(Ping-Ning Hsu),李建國(Chien-Kuo Lee) | |
| dc.subject.keyword | 肺部幹細胞/前驅幹細胞,氣喘,呼吸道發炎, | zh_TW |
| dc.subject.keyword | Pulmonary stem/progenitor cell,asthma,airway inflammation, | en |
| dc.relation.page | 74 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2015-03-27 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-104-1.pdf | 11.21 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。