請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/83499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 | Jing-Hui Huang | en |
| dc.contributor.author | 黃靖惠 | zh_TW |
| dc.date.accessioned | 2023-03-19T21:09:00Z | - |
| dc.date.copyright | 2022-10-05 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-06 | |
| dc.identifier.citation | 1. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775-87. 2. Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF. Cutting Edge: TGF-β induces a regulatory phenotype in CD4+CD25? T cells through Foxp3 induction and down-regulation of Smad7. J Immunol. 2004;172(9):5149-53. 3. Podojil JR, Liu LN, Marshall SA, Chiang M-Y, Goings GE, Chen L, et al. B7-H4Ig inhibits mouse and human T-cell function and treats EAE via IL-10/Treg-dependent mechanisms. J Autoimmun. 2013;44:71-81. 4. Vignali DAA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8(7):523-32. 5. Asseman C, Mauze, S. L, M. W. C, R. L. & Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med. 1999;190(7):995–1004. 6. Sierro S, Romero P, Speiser DE. The CD4-like molecule LAG-3, biology and therapeutic applications. Expert Opin Ther Targets. 2010;15(1):91-101. 7. Li D-Y, Xiong X-Z. ICOS+ Tregs: A functional subset of Tregs in immune diseases. Front Immunol. 2020;11. 8. Yao Y, Vent-Schmidt J, McGeough MD, Wong M, Hoffman HM, Steiner TS, et al. Tr1 cells, but not Foxp3? regulatory T cells, suppress NLRP3 inflammasome activation via an IL-10-dependent mechanism. J Immunol. 2015;195(2):488-97. 9. Machteld M. Tiemessen, Ann L. Jagger, Hayley G. Evans, Martijn J. C. van Herwijnen, Susan John, Taams LS. CD4+ CD25+ Foxp3+ regulatory T cells induce alternative activation of human monocytes:macrophages. PNAS. 2007;104:19446–51. 10. Marco Romano, Giorgia Fanelli, Nicole Tan, Nova-Lamperti E, McGregor R, Robert I. Lechler, et al. Expanded regulatory T cells induce alternatively activated monocytes with a reduced capacity to expand T helper-17 Cells. Front Immunol. 2018;9:1625. 11. Andersson SE, Eneljung T, Tengvall S, Jirholt P, Stern A, Henningsson L, et al. Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis. Arthritis Res Ther. 2016;18(1):140-51. 12. Ashour HM, Niederkorn JY. Peripheral tolerance via the anterior chamber of the eye: role of B cells in MHC class I and II antigen presentation. J Immunol. 2006;176(10):5950-7. 13. Sun JB, Flach CF, Czerkinsky C, Holmgren J. B lymphocytes promote expansion of regulatory T cells in oral tolerance: powerful induction by antigen coupled to cholera toxin B subunit. J Immunol. 2008;181(12):8278-87. 14. D.Wolf BS, Dittel BN, Hardardottir F, Charles A. Janeway J. Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J Exp Med. 1996;184:2271-8. 15. Shah S, Qiao L. Resting B cells expand a CD4?CD25?Foxp3? Treg population via TGF-β3. Eur J Immunol. 2008;38(9):2488-98. 16. Chen X, Jensen PE. Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3? CD4 T cells. J Immunol. 2007;179(4):2046-50. 17. Chen LC, Delgado JC, Jensen PE, Chen X. Direct expansion of human allospecific FoxP3?CD4?regulatory T cells with allogeneic B cells for therapeutic application. J Immunol. 2009;183(6):4094-102. 18. Lu FT, Yang W, Wang Y-H, Ma H-D, Tang W, Yang J-B, et al. Thymic B cells promote thymus-derived regulatory T cell development and proliferation. J Autoimmun. 2015;61:62-72. 19. Reichardt P, Dornbach B, Rong S, Beissert S, Gueler F, Loser K, et al. Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse. Blood. 2007;110(5):1519-29. 20. Chien C-H, Chiang B-L. Regulatory T cells induced by B cells: a novel subpopulation of regulatory T cells. J Biomed Sci. 2017;24(1):86-93. 21. Chien C-H, Chiang B-L. Recent advances in regulatory T cells induced by B cells. Cell Mol Immunol. 2017;15(5):539-41. 22. Hsu L-H, Li K-P, Chu K-H, Chiang B-L. A B-1a cell subset induces Foxp3? T cells with regulatory activity through an IL-10-independent pathway. Cell Mol Immunol. 2014;12(3):354-65. 23. Chu KH, Chiang BL. Regulatory T cells induced by mucosal B cells alleviate allergic airway hypersensitivity. Am J Respir Cell Mol Biol. 2012;46(5):651-9. 24. Chen S-Y, Hsu W-T, Chen Y-L, Chien C-H, Chiang B-L. Lymphocyte-activation gene 3?(LAG3) forkhead box protein 3? (FOXP3? ) regulatory T cells induced by B cells alleviates jointinflammation in collagen-induced arthritis. J Autoimmun. 2016;68:75-85. 25. Shao T-Y, Hsu L-H, Chien C-H, Chiang B-L. Novel Foxp3? IL-10? regulatory T-cells induced by B-cells alleviate intestinal inflammation in vivo. Sci Rep. 2016;6(1):32415-24. 26. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496(7446):445-55. 27. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5(12):953-64. 28. George Kolios VV, Elias Kouroumalis. Role of Kupffer cells in the pathogenesis of liver disease. World J Gastroenterol. 2006;12:7413-20. 29. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11(11):723-37. 30. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122(3):787-95. 31. Meda Spaccamela V, Valencia RG, Pastukhov O, Duppenthaler A, Dettmer MS, Erb J, et al. High levels of IL-18 and IFN-γ in chronically inflamed tissue in chronic granulomatous disease. Front Immunol. 2019;10. 32. Ferrante CJ, Leibovich SJ. Regulation of macrophage polarization and wound healing. Adv Wound Care. 2012;1(1):10-6. 33. Platt AM, Bain CC, Bordon Y, Sester DP, Mowat AM. An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation. J Immunol. 2010;184(12):6843-54. 34. Szekanecza Zn, Koch AE. Macrophages and their products in rheumatoid arthritis. Curr Opin Rheumatol. 2007;19:289-95. 35. Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009;10(11):1178-84. 36. Rivollier A, He J, Kole A, Valatas V, Kelsall BL. Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J Exp Med. 2012;209(1):139-55. 37. Xuan W, Qu Q, Zheng B, Xiong S, Fan G-H. The chemotaxis of M1 and M2 macrophages is regulated by different chemokines. J Leukocyte Biol. 2015;97(1):61-9. 38. R?szer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm. 2015;2015:1-16. 39. Gundra UM, Girgis NM, Ruckerl D, Jenkins S, Ward LN, Kurtz ZD, et al. Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct. Blood. 2014;123(20):e110-e22. 40. Yao Y, Xu X-H, Jin L. Macrophage polarization in physiological and pathological pregnancy. Front Immunol. 2019;10. 41. Murray PJ. Macrophage polarization. Annu Rev Physiol. 2017;79(1):541-66. 42. Zhang H, Wu X, Wang G, Liu P, Qin S, Xu K, et al. Macrophage polarization, inflammatory signaling, and NF-κB activation in response to chemically modified titanium surfaces. Colloids Surf B Biointerfaces. 2018;166:269-76. 43. Li L, Wei C, Cai S, Fang L. TRPM7 modulates macrophage polarization by STAT1/STAT6 pathways in RAW264.7?cells. Biochem Biophys Res Commun. 2020;533(4):692-7. 44. Tugal D, Liao X, Jain MK. Transcriptional control of macrophage polarization. Atertio Thromb Vasc Biol. 2013;33(6):1135-44. 45. Gong M, Zhuo X, Ma A. STAT6 upregulation promotes M2 macrophage polarization to suppress atherosclerosis. Med Sci Monit. 2017;23:240-9. 46. Yu T, Gan S, Zhu Q, Dai D, Li N, Wang H, et al. Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24. Nat Commun. 2019;10(1). 47. Raes G, Van den Bergh R, De Baetselier P, Ghassabeh GH. Arginase-1 and Ym1 are markers for murine, but not human, alternatively activated myeloid cells. J Immunol. 2005;174(11):6561-2. 48. Swanson KV, Deng M, Ting JPY. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477-89. 49. Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821-32. 50. Patel MN, Carroll RG, Galvan-Pena S, Mills EL, Olden R, Triantafilou M, et al. Inflammasome priming in sterile inflammatory disease. Trends Mol Med. 2017;23(2):165-80. 51. Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16(7):407-20. 52. He Y, Hara H, Nunez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci. 2016;41(12):1012-21. 53. Lord?n G, Sanju?n-Garc?a I, de Pablo N, Meana C, Alvarez-Miguel I, P?rez-Garc?a MT, et al. Lipin-2 regulates NLRP3 inflammasome by affecting P2X7 receptor activation. J Exp Med. 2017;214(2):511-28. 54. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol. 2009;183(2):787-91. 55. Malik A, Kanneganti T-D. Inflammasome activation and assembly at a glance. J Cell Sci. 2017;130(23):3955-63. 56. Aizawa E, Karasawa T, Watanabe S, Komada T, Kimura H, Kamata R, et al. GSDME-dependent incomplete pyroptosis permits selective IL-1α release under caspase-1 inhibition. iScience. 2020;23(5):101070-85. 57. He Y, Zeng MY, Yang D, Motro B, N??ez G. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature. 2016;530(7590):354-7. 58. Shi H, Wang Y, Li X, Zhan X, Tang M, Fina M, et al. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component. Nat Immunol. 2015;17(3):250-8. 59. Inoue M, Shinohara ML. NLRP3 inflammasome and MS/EAE. Autoimmune Dis. 2013;2013:1-8. 60. Yin Z, Deng T, Peterson LE, Yu R, Lin J, Hamilton DJ, et al. Transcriptome analysis of human adipocytes implicates the NOD-like receptor pathway in obesity-induced adipose inflammation. Mol Cell Endocrinol. 2014;394(1-2):80-7. 61. Stienstra R, Joosten LAB, Koenen T, van Tits B, van Diepen JA, van den Berg SAA, et al. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab. 2010;12(6):593-605. 62. Jenko B, Praprotnik S, Tom?i? M, Dol?an V. NLRP3 and CARD8 polymorphisms influence higher disease activity in rheumatoid arthritis. J Med Biochem. 2016;35(3):319-23. 63. Mathews RJ, Robinson JI, Battellino M, Wong C, Taylor JC, Eyre S, et al. Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment. Ann Rheum Dis. 2014;73(6):1202-10. 64. Rosengren S. Expression and regulation of cryopyrin and related proteins in rheumatoid arthritis synovium. Ann Rheum Dis. 2005;64(5):708-14. 65. Choulaki C, Papadaki G, Repa A, Kampouraki E, Kambas K, Ritis K, et al. Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis. Arthritis Res Ther. 2015;17(1). 66. Zhang H, Wang S, Huang Y, Wang H, Zhao J, Gaskin F, et al. Myeloid-derived suppressor cells are proinflammatory and regulate collagen-induced arthritis through manipulating Th17 cell differentiation. Clin Immunol. 2015;157(2):175-86. 67. Roberto Furlan, Gianvito Martino, Francesca Galbiati, Pietro L. Poliani, Simona Smiroldo, Alessendra Bergami, et al. Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. J Immunol. 1999;163:2403-9. 68. Shi F-D, Takeda K, Akira S, Sarvetnick N, Ljunggren H-G. IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-γ by NK cells. J Immunol. 2000;165(6):3099-104. 69. Gris D, Ye Z, Iocca HA, Wen H, Craven RR, Gris P, et al. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol. 2010;185(2):974-81. 70. Webb R, Jeffries M, Sawalha AH. Uric acid directly promotes human T-cell activation. Am J Med Sci. 2009;337(1):23-7. 71. Lee S-J, Nam K-I, Jin H-M, Cho Y-N, Lee S-E, Kim T-J, et al. Bone destruction by receptor activator of nuclear factor κB ligand-expressing T cells in chronic gouty arthritis. Arthritis Res Ther. 2011;13(5):R164. 72. Ragab G, Elshahaly M, Bardin T. Gout: an old disease in new perspective - a review. J Adv Res. 2017;8(5):495-511. 73. Schumacher HR, Berger MF, Li-Yu J, Perez-Ruiz F, Burgos-Vargas R, Li C. Efficacy and tolerability of celecoxib in the treatment of acute gouty arthritis: a randomized controlled trial. J Rheumatol. 2012;39(9):1859-66. 74. Cavalli G, Dinarello CA. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology. 2015:kev269. 75. Torres RJ, Puig JG. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J Rare Dis. 2007;2(1). 76. Reginato AM, Olsen BR. Genetics and experimental models of crystal-induced arthritis. Lessons learned from mice and men- is it crystal clear? Curr Opin Rheumatol. 2007;19:134-45. 77. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357-61. 78. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008;9(8):847-56. 79. Catherine Dostert, Virginie P?trilli, Robin Van Bruggen, Chad Steele, Mossma BT, Tschopp Jr. Innate immune activation through nalp3 inflammasome sensing of asbestos and silica. Science. 2008;320(5876):674–7. 80. Gombault A, Baron L, Couillin I. ATP release and purinergic signaling in NLRP3 inflammasome activation. Front Immunol. 2013;3. 81. Fritz JH, Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Apostolidou E, et al. Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One. 2011;6(12):e29318. 82. Moos S, Mohebiany AN, Waisman A, Kurschus FC. Imiquimod-induced psoriasis in mice depends on the IL-17 signaling of keratinocytes. J Investig Dermatol Symp Proc. 2019;139(5):1110-7. 83. Lin S-H, Chuang H-Y, Ho J-C, Lee C-H, Hsiao C-C. Treatment with TNF-α inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation. J Dermatol Sci. 2018;91(3):276-84. 84. Oord JJvd, Wolf-Peeters Cd. Epithelium-lining macrophages in psoriasis. Br J Dermatol. 1994 130(5):589-94. 85. Wang H, Peters T, Kess D, Sindrilaru A, Oreshkova T, Rooijen NV, et al. Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation. J Clin Invest. 2006;116(8):2105-14. 86. Sun C, Sun L, Ma H, Peng J, Zhen Y, Duan K, et al. The phenotype and functional alterations of macrophages in mice with hyperglycemia for long term. J Cell Physiol. 2012;227(4):1670-9. 87. Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201(6):1605-13. 88. Kamata M, Tada Y. Dendritic cells and macrophages in the pathogenesis of psoriasis. Front Immunol. 2022;13. 89. Kim T-G, Kim DS, Kim H-P, Lee M-G. The pathophysiological role of dendritic cell subsets in psoriasis. BMB Rep. 2014;47(2):60-8. 90. Sch?n MP. Adaptive and innate immunity in psoriasis and other inflammatory disorders. Front Immunol. 2019;10. 91. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, Abello MV, Novitskaya I, Pierson KC, et al. Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. J Investig Dermatol Symp Proc. 2009;129(1):79-88. 92. Ueyama A, Yamamoto M, Tsujii K, Furue Y, Imura C, Shichijo M, et al. Mechanism of pathogenesis of imiquimod-induced skin inflammation in the mouse: A role for interferon-alpha in dendritic cell activation by imiquimod. J Dermatol. 2014;41(2):135-43. 93. van der Fits L, Mourits S, Voerman JSA, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182(9):5836-45. 94. Stratis A. Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation. J Clin Invest. 2006;116(8):2094-104. 95. Mease PJ. Inhibition of interleukin-17, interleukin-23 and the Th17 cell pathway in the treatment of psoriatic arthritis and psoriasis. Curr Opin Rheumatol. 2015;27(2):127-33. 96. Lai H-C, Awad F, Assrawi E, Jumeau C, Georgin-Lavialle S, Cobret L, et al. Impact of human monocyte and macrophage polarization on NLR expression and NLRP3 inflammasome activation. PLoS One. 2017;12(4):e0175336. 97. Torres R, Macdonald L, Croll SD, Reinhardt J, Dore A, Stevens S, et al. Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis. Ann Rheum Dis. 2009;68(10):1602-8. 98. Antonioli L, Pacher P, Vizi ES, Hask? G. CD39 and CD73 in immunity and inflammation. Trends Mol Med. 2013;19(6):355-67. 99. Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Front Immunol. 2014;5. 100. Prasad S, Ewigman B, Hickner J. Acute gout- oral steroids work as well as NSAIDs. . J Fam Pract. 2008;57(10):655-7. 101. Wang L, Ray A, Jiang X, Wang Jy, Basu S, Liu X, et al. T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis. Mucosal Immunol. 2015;8(6):1297-312. 102. Chien C-H, Yu H-H, Chiang B-L. Single allergen-induced oral tolerance inhibits airway inflammation in conjugated allergen immunized mice. J Allergy Clin Immunol. 2015;136(4):1110-3.e4. 103. Kanamori M, Nakatsukasa H, Okada M, Lu Q, Yoshimura A. Induced regulatory T cells: their development, stability, and applications. Trends Immunol. 2016;37(11):803-11. 104. Waisman A, Etemire E, Krull M, Hasenberg M, Reichardt P, Gunzer M. Transiently reduced PI3K/Akt activity drives the development of regulatory function in antigen-stimulated nave T-cells. PLoS One. 2013;8(7):e68378. 105. Guarda G, Dostert C, Staehli F, Cabalzar K, Castillo R, Tardivel A, et al. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature. 2009;460(7252):269-73. 106. Chien C-H, Yu H-C, Chen S-Y, Chiang B-L. Characterization of c-Maf ? Foxp3? regulatory T cells induced by repeated stimulation of antigen-presenting B cells. Sci Rep. 2017;7(1):46348-56. 107. Gagliani N, Magnani CF, Huber S, Gianolini ME, Pala M, Licona-Limon P, et al. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 2013;19(6):739-46. 108. Robert M. Hoek, Sigrid R. Ruuls, Craig A. Murphy, Gavin J. Wright, Ruth Goddard, Sandra M. Zurawski, et al. Down-Regulation of the Macrophage Lineage Through Interaction with OX2 (CD200). Science. 2000;290:1768-71. 109. Lord?n G, Sanju?n-Garc?a I, de Pablo N, Meana C, Alvarez-Miguel I, P?rez-Garc?a MT, et al. Lipin-2 regulates NLRP3 inflammasome by affecting P2X7 receptor activation. J Exp Med. 2017;214(2):511-28. 110. Franchi L, Eigenbrod T, Nunez G. Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol. 2009;183(2):792-6. 111. Franchi L, et al. Sensing and reacting to microbes through the inflammasomes. Nat Immunol. 2012;13:325-32. 112. Machteld M. Tiemessen, Ann L. Jagger, Hayley G. Evans, Martijn J. C. van Herwijnen, Susan John, Taams LS. CD4+CD25+Foxp3+regulatory T cells induce alternative activation of human monocytes:macrophages. PNAS. 2007;104:19446–51. 113. Legrand-Poels S, Esser N, L’homme L, Scheen A, Paquot N, Piette J. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes. Biochem Pharmacol. 2014;92(1):131-41. 114. Cleophas MCP, Cri?an TO, Lemmers H, Toenhake-Dijkstra H, Fossati G, Jansen TL, et al. Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases. Ann Rheum Dis. 2016;75(3):593-600. 115. Zaki MH, Lamkanfi M, Kanneganti TD. The Nlrp3 inflammasome: contributions to intestinal homeostasis. Trends Immunol. 2011;32(4):171-9. 116. Perricone C, Triggianese P, Bartoloni E, Cafaro G, Bonifacio AF, Bursi R, et al. The anti-viral facet of anti-rheumatic drugs: lessons from COVID-19. J Autoimmun. 2020;111:102468. 117. Yang C-A, Chiang B-L. Inflammasomes and human autoimmunity: a comprehensive review. J Autoimmun. 2015;61:1-8. 118. Wang J, Yang Q, Zhang Q, Yin C, Zhou L, Zhou J, et al. Invariant natural killer T cells ameliorate monosodium urate crystal-induced gouty in ammation in mice. Front Immunol. 2017;8:1710-7. 119. Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2):327-31. 120. Cronstein BN, Terkeltaub R. The inflammatory process of gout and its treatment. Arthritis Res Ther. 2006;8:S3. 121. Yin W, Zhou Q-L, OuYang S-X, Chen Y, Gong Y-T, Liang Y-M. Uric acid regulates NLRP3/IL-1β signaling pathway and further induces vascular endothelial cells injury in early CKD through ROS activation and K+ efflux. BMC Nephrol. 2019;20(1). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/83499 | - |
| dc.description.abstract | 巨噬細胞的過度活化與許多發炎疾病息息相關，像是痛風，糖尿病，乾癬症。因此若能並且給於適當的控制巨噬細胞的活化將會是治療發炎疾病重要的方法之一。近年來，研究結果發現，B 細胞誘導的調節性T 細胞，稱為Treg-of-B 細胞，具有表現出與調節性T 細胞相似的蛋白，並且具有調節後天免疫的能力，像是抑制T細胞的增生、第一型輔助性T細胞以及第十七型輔助性T 細胞的免疫反應。然而，關於Treg-of-B cells 是否調控先天免疫反應尚未探討。本篇研究的目的為探討Treg-of-B是否具有調控巨噬細胞的功能。 在研究結果中，我們發現在體外實驗 Treg-of-B 細胞，而非tTreg 或是effector T 細胞，方會抑制 LPS/ATP 刺激巨噬細胞引起的發炎體活化, 包括抑制IL-1 分泌, caspase-1 活化, 以及 NLRP3 的產生，並且是透過Treg-of-B 細胞與巨噬細胞之間的細胞接觸達到抑制的功; 我們更進一步發現Treg-of-B 細胞 藉由抑制NF-B 的活化來達到抑制巨噬細胞NLRP3 發炎體的活化。 由於之前的研究指出, M2 巨噬細胞NLRP3 發炎體相關的蛋白以及mRNA 表現會受到抑制，因此我們更進一步探討Treg-of-B 是否會影響巨噬細胞的極化。實驗結果發現，當巨噬細胞與Treg-of-B共同培養時，即使受到LPS/IFN- 的刺激，Treg-of-B細胞仍然會誘發巨噬細胞表現典型的M2 相關標記，像是Arg-1 、IL-10、Pdcd1lg2、MGL-1、IL-4、YM1/2、及CD206; 進一步探討機制的結果顯示，Treg-of-B 會藉由與巨噬細胞的細胞接觸，誘導巨噬細胞STAT6 的磷酸化,並且，實驗結果顯示在STAT6 缺陷的巨噬細胞，與Treg-of-B共同培養時，不能誘導巨噬細胞表現M2 相關標記。以上的結果證明Treg-of-B 細胞會藉由活化STAT6 的表現，進而促進M2 巨噬細胞的極化。 此外，我們建立小鼠皮下氣囊模式，探討尿酸結晶誘導NLRP3活化的發炎反應, 結果顯示Treg-of-B 細胞移植到小鼠體內能有效地減少發炎激素IL-1、 CXCL1、、及CCL2的產生，以及嗜中性球與單核球的浸潤。在痛風的動物模式中，我們觀察到, 浸潤囊腔的組織中Treg-of-B 細胞與巨噬細胞有細胞接觸的現象。因此，當小鼠受到尿酸結晶刺激時，Treg-of-B 細胞會移動到囊腔的組織，進一步抑制巨噬細胞NLRP3 發炎體的活化，減緩痛風疾病的發生。 另外，我們將Treg-of-B 誘導的M2 巨噬細胞以尾靜脈的方式給予小鼠，能夠有效的緩解imiquimod 誘導的小鼠乾癬症的病症，像是減緩小鼠皮膚的紅斑以及脫屑的現象。除此之外，給予Treg-of-B 誘導的M2 巨噬細胞能有效的抑制皮膚組織的IL-17F表現，以及抑制鄰近淋巴結細胞在體外刺激時分泌IL-22、IL-17、IFN-; 因此Treg-of-B cell 誘導的 M2 巨噬細胞, 會藉由減少局部以及系統性的發炎反應，達到減緩乾癬症。 綜合以上的實驗結果顯示，脾臟的B細胞所誘導的調節性T細胞能藉由抑制NLRP3 發炎體的活化, 以及誘導出M2 巨噬細胞, 來達到調控先天免疫的功能。此研究也提供未來使用Treg-of-B細胞治療發炎性或其他自體免疫疾病的潛力。 | zh_TW |
| dc.description.abstract | The excess activation of macrophage is associated with several inflammatory diseases, such as gouty arthritis, diabetes, and psoriasis. Hence, the proper regulation of the macrophage activation will be an important therapeutic strategy for inflammatory diseases. Recently, we identified a population of Foxp3- regulatory T cells that were induced by B cells, named Treg-of-B cells, which exert regulatory functions in adaptive immunity, including inhibition of Th1 and Th17-mediated immune responses. However, whether Treg-of-B cells regulate innate immunity remains unclear. This study aimed to investigate whether Treg-of-B cells could regulate macrophage function and differentiation. We showed that Treg-of-B cells, but not thymus-derived Treg or effector T cells, inhibited inflammasome-mediated IL-1 secretion, caspase-1 activation, and NLRP3 production by LPS/ATP stimulation in a cell contact-dependent manner. In addition, Treg-of-B cells inhibited monosodium urate-induced NLRP3 inflammasome activation in vitro via NF-B signaling. Previous study indicated that the induction of NLRP3-associated protein and mRNA expression is inhibited in M2 macrophages. Next, we further explored whether Treg-of-B cells could promote alternatively activated macrophage (M2 macrophages) polarization. The macrophages co-cultured with Treg-of-B cells upregulated typical M2-associated molecules, including Arg1, Il10, Pdcd1lg2, Mgl-1, Il4, Ym1/2 and Cd206 under M1 polarization condition. Further investigation of the molecular mechanism revealed that Treg-of-B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact-dependent manner. Adoptive transfer of Treg-of-B cells ameliorated gouty inflammation in a mouse air pouch model through reducing neutrophil and leukocyte influx. Moreover, the mice intravenous receiving Treg-of-B cells had significantly lower levels of IL-1, CXCL1, and CCL2 compared to MSU-treated control mice. We also found that infiltrated Treg-of-B contacted with local macrophages, but not neutrophils in the tissue of air pouch. Therefore, Treg-of-B cells immediately migrated to air pouch and inhibited NLRP3 inflammasome activation, resulting in the amelioration of gouty arthritis upon MSU stimulation. Adoptive transfer of Treg-of-B-induced M2 macrophages in imiquimod-induced psoriasis mice alleviated skin inflammation such as reducing the erythema and scaling. Moreover, IL-17F mRNA expression in skin lesions was significantly decreased in Treg-of-B-induced-M2 macrophages treatment group. In addition, IL-22 and IFN-γ, and IL-17 production by immune cells in the draining lymph nodes was significantly reduced in the Treg-of-B-induced M2 groups. Therefore, Treg-of-B cell-induced M2 macrophages ameliorated manifestations of psoriasis by reducing local and systemic inflammation. Overall, our results demonstrated that Treg-of-B cells exerted regulatory effects on innate immunity by suppressing NLRP3 inflammasome activation and inducing alternatively activated macrophages, providing a cell-based therapeutic strategy for inflammatory diseases and autoimmunity diseases. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T21:09:00Z (GMT). No. of bitstreams: 1 U0001-2908202200584200.pdf: 29793239 bytes, checksum: 30af2a7ac021055fc691e428723f16ff (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書 i 致謝 ii 中文摘要 iv Abstract vi Abbreviations viii Chapter 1. Introduction 1 1.1 Naturally occurring Treg cells and inducible Treg cells 2 1.2 The suppressive function of Treg cells 2 1.3 Regulatory T cells induced by B cells 3 1.4 Macrophages 4 1.4.1 Macrophage in inflammation 5 1.4.2 Macrophage in inflammatory disease 5 1.4.3 The polarization of macrophages 6 1.5 The inflammasome 7 1.5.1 NLRP3 7 1.5.2 The diseases associated with NLRP3 inflammasome 9 1.6 Gouty arthritis 9 1.6.1 Introduction 10 1.6.2 Risk factors of Gout 11 1.6.3 Mechanism of Gout 11 1.7 Psoriasis 12 1.7.1 Introduction 12 1.7.2 The mechanisms of psoriasis 12 1.7.2.1 macrophage 13 1.7.2.2 Th1 and Th17 13 1.8 Specific Aim 14 1.8.1 To investigate whether Treg-of-B cells could regulate macrophage function 14 1.8.2 To investigate whether Treg-of-B cells could alleviate macrophage-associated disease. 15 Chapter 2. Material and Methods 16 2.1 Animals 17 2.2 The induction of Treg-of-B cells 17 2.3 The generation of Tr1 cells 18 2.4 In vitro coculture experiments for inflammasome activation 18 2.5 The proliferative response of T cells 19 2.6 In vitro co-culture system for M2 polarization 19 2.7 ELISA 20 2.8 RT-PCR 21 2.9 Bone marrow-derived macrophage and peritoneal macrophage isolation 21 2.10 Western blotting 21 2.11 Haematoxylin and eosin staining analysis and scoring system 22 2.12 Air pouch model and adoptive transfer of Treg-of-B cells 23 2.13 The distribution of Treg-of-B cells 23 2.14 The infiltrated Treg-of-B cells engaged in local macrophages. 24 2.15 IMQ model and adoptive transfer of Treg-of-B cell-induced M2 macrophages 24 2.16 Flow cytometric analysis 25 2.17 Statistical analysis 25 Chapter 3. Results 26 3.1 The phenotype and characteristics of Foxp3– Tregs induced by splenic B cells 27 3.2 Treg-of-B cells modulate macrophages activation 27 3.2.1 Treg-of-B cells suppressed NLRP3 inflammasome activation upon LPS and ATP stimulation 27 3.2.2 Treg-of-B cells suppressed inflammasome activation mainly via a contact-dependent mechanism 28 3.2.3 IL-10 did not play a crucial role in the suppressing NLRP3 inflammasome by Treg-of-B cells 29 3.2.4 Treg-of-B cells suppressed inflammasome activation predominantly via a contact-dependent mechanism 29 3.2.5 Treg-of-B cells inhibited MSU-Induced NLRP3 inflammasome activation in a cell contact-dependent manner 31 3.2.6 Treg-of-B cells inhibited MSU-induced NLRP3 inflammasome activation by repressing NF-B signaling 33 3.3 Treg-of-B cells regulated the macrophage phenotype polarization. 33 3.3.1 Treg-of-B cells induce M2 macrophage polarization 33 3.3.2 Treg-of-B cells induced tolerogenic M2-like macrophage programming by activating STAT6 35 3.3.3 STAT6 in BMDMs was critical for the induction of M2 macrophages by Treg-of-B cells, but no effect on macrophage activation 36 3.4 Treg-of-B cells suppressed NLRP3 inflammasome-associated disease in vivo. 37 3.4.1 Treg-of-B cells suppressed gouty inflammation in vivo 37 3.4.2 Treg-of-B cells migrated to the air pouch and draining lymph nodes and regulated local inflammation in gout 39 3.4.3 The infiltrated Treg-of-B engage in physical contacts with local macrophages 39 3.5 Treg-of-B cells could promote alternatively activated macrophage polarization and alleviate M1 macrophage-associated inflammatory disease 40 3.5.1 Treg-of-B-induced M2 macrophages ameliorate skin inflammation in a mouse model of psoriasis 40 Chapter 4. Discussions and Conclusions 43 Chapter 5. Perspectives 51 Chapter 6. References 54 Chapter 7. Figures and Tables 70 Appendix 135 | |
| dc.language.iso | en | |
| dc.subject | 乾癬症 | zh_TW |
| dc.subject | 發炎體 | zh_TW |
| dc.subject | B細胞所誘導的調節性T細胞 | zh_TW |
| dc.subject | 巨噬細胞 | zh_TW |
| dc.subject | 痛風 | zh_TW |
| dc.subject | Treg-of-B | en |
| dc.subject | psoriasis | en |
| dc.subject | gouty | en |
| dc.subject | macrophage | en |
| dc.subject | inflammasome | en |
| dc.title | B 細胞誘導調節性T 細胞對先天免疫細胞的調控機制研究 | zh_TW |
| dc.title | Study on the Modulation of Innate Immune Responses by Regulatory T Cells Induced by B Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 莊雅惠(Ya-Hui Chuang),孫昭玲(Jau-Ling Suen),楊皇煜(Huang-Yu Yang),賈景山(Jean-San Chia) | |
| dc.subject.keyword | 發炎體,B細胞所誘導的調節性T細胞,巨噬細胞,痛風,乾癬症, | zh_TW |
| dc.subject.keyword | inflammasome,Treg-of-B,macrophage,gouty,psoriasis, | en |
| dc.relation.page | 135 | |
| dc.identifier.doi | 10.6342/NTU202202905 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2022-09-06 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2908202200584200.pdf 未授權公開取用 | 29.09 MB | Adobe PDF |
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。