Location of CD4+ T cell priming regulates the differentiation of Th1 and Th17 cells and their contribution to arthritis

Journal of Immunology

Volumn 190, Issue 11, 2013, Pages 5423-5435

  Rodeghero, Rachel ^a   Cao, Yanxia ^a   Olalekan, Susan A ^a   Iwakua, Yoichiro ^b   Glant, Tibor T ^a   Finnegan, Alison ^a  

^a RUSH UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 17; PROTEOGLYCAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTHRITIS; ARTICLE; CD4+ T LYMPHOCYTE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RESPONSE; FEMALE; HISTOLOGY; IMMUNIZATION; JOINT; LYMPH NODE; LYMPHOCYTE DIFFERENTIATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; SPLEEN; TH1 CELL; TH17 CELL;

ANIMALS; ANTIGEN-PRESENTING CELLS; ANTIGENS; ARTHRITIS, EXPERIMENTAL; CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; CYTOKINES; DENDRITIC CELLS; FEMALE; HUMANS; INTERFERON-GAMMA; INTERLEUKIN-17; LYMPH NODES; LYMPHOCYTE ACTIVATION; MICE; MICE, KNOCKOUT; PROTEOGLYCANS; TH1 CELLS; TH17 CELLS;

EID: 84878079930     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1203045     Document Type: Article

References (80)

1. Goronzy, J. J., and C. M. Weyand. 2005. Rheumatoid arthritis. Immunol. Rev. 204: 55-73. (Pubitemid 40460493)
2. Tak, P. P. 2012. A personalized medicine approach to biologic treatment of rheumatoid arthritis: a preliminary treatment algorithm. Rheumatology (Oxford) 51: 600-609.
3. Weyand, C. M., K. C. Hicok, D. L. Conn, and J. J. Goronzy. 1992. The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Ann. Intern. Med. 117: 801-806.
4. Zhu, J., H. Yamane, and W. E. Paul. 2010. Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 28: 445-489.
5. Szabo, S. J., S. T. Kim, G. L. Costa, X. Zhang, C. G. Fathman, and L. H. Glimcher. 2000. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669.
6. Afkarian, M., J. R. Sedy, J. Yang, N. G. Jacobson, N. Cereb, S. Y. Yang, T. L. Murphy, and K. M. Murphy. 2002. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat. Immunol. 3: 549-557. (Pubitemid 34662307)
7. Kaplan, M. H., Y. L. Sun, T. Hoey, and M. J. Grusby. 1996. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382: 174-177. (Pubitemid 26242885)
8. Veldhoen, M., R. J. Hocking, C. J. Atkins, R. M. Locksley, and B. Stockinger. 2006. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24: 179-189. (Pubitemid 43214587)
9. H-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8: 967-974.
10. Nurieva, R., X. O. Yang, G. Martinez, Y. Zhang, A. D. Panopoulos, L. Ma, K. Schluns, Q. Tian, S. S. Watowich, A. M. Jetten, and C. Dong. 2007. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448: 480-483. (Pubitemid 47123514)
11. Chung, Y., S. H. Chang, G. J. Martinez, X. O. Yang, R. Nurieva, H. S. Kang, L. Ma, S. S. Watowich, A. M. Jetten, Q. Tian, and C. Dong. 2009. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30: 576-587.
12. Ivanov, I. I., B. S. McKenzie, L. Zhou, C. E. Tadokoro, A. Lepelley, J. J. Lafaille, D. J. Cua, and D. R. Littman. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121-1133. (Pubitemid 44380299)
13. Yang, Y., A. R. Gocke, A. Lovett-Racke, P. D. Drew, and M. K. Racke. 2008. PPARα regulation of the immune response and autoimmune encephalomyelitis. PPAR Res. 2008: 546753.
14. H17-dependent autoimmunity. J. Immunol. 179: 4313-4317.
15. Yang, X. O., A. D. Panopoulos, R. Nurieva, S. H. Chang, D. Wang, S. S. Watowich, and C. Dong. 2007. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J. Biol. Chem. 282: 9358-9363. (Pubitemid 47104613)
16. Finnegan, A., K. Mikecz, P. Tao, and T. T. Glant. 1999. Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines. J. Immunol. 163: 5383-5390.
17. Finnegan, A., M. J. Grusby, C. D. Kaplan, S. K. O'Neill, H. Eibel, T. Koreny, M. Czipri, K. Mikecz, and J. Zhang. 2002. IL-4 and IL-12 regulate proteoglycan-induced arthritis through Stat-dependent mechanisms. J. Immunol. 169: 3345-3352. (Pubitemid 35013184)
18. Cao, Y., P. D. Doodes, T. T. Glant, and A. Finnegan. 2008. IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J. Immunol. 180: 922-930.
19. Doodes, P. D., Y. Cao, K. M. Hamel, Y. Wang, B. Farkas, Y. Iwakura, and A. Finnegan. 2008. Development of proteoglycan-induced arthritis is independent of IL-17. J. Immunol. 181: 329-337.
20. Vermeire, K., H. Heremans, M. Vandeputte, S. Huang, A. Billiau, and P. Matthys. 1997. Accelerated collagen-induced arthritis in IFN-γ receptor-deficient mice. J. Immunol. 158: 5507-5513. (Pubitemid 127681260)
21. Manoury-Schwartz, B., G. Chiocchia, N. Bessis, O. Abehsira-Amar, F. Batteux, S. Muller, S. Huang, M. C. Boissier, and C. Fournier. 1997. High susceptibility to collagen-induced arthritis in mice lacking IFN-γ receptors. J. Immunol. 158: 5501-5506. (Pubitemid 127681259)
22. Willenborg, D. O., S. Fordham, C. C. Bernard, W. B. Cowden, and I. A. Ramshaw. 1996. IFN-γ plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J. Immunol. 157: 3223-3227. (Pubitemid 126449130)
23. Ferber, I. A., S. Brocke, C. Taylor-Edwards, W. Ridgway, C. Dinisco, L. Steinman, D. Dalton, and C. G. Fathman. 1996. Mice with a disrupted IFN-γ gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J. Immunol. 156: 5-7.
24. Caspi, R. R., C. C. Chan, B. G. Grubbs, P. B. Silver, B. Wiggert, C. F. Parsa, S. Bahmanyar, A. Billiau, and H. Heremans. 1994. Endogenous systemic IFN-γ has a protective role against ocular autoimmunity in mice. J. Immunol. 152: 890-899.
25. Cruz, A., S. A. Khader, E. Torrado, A. Fraga, J. E. Pearl, J. Pedrosa, A. M. Cooper, and A. G. Castro. 2006. Cutting edge: IFN-γ regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection. J. Immunol. 177: 1416-1420. (Pubitemid 44092473)
26. Park, H., Z. Li, X. O. Yang, S. H. Chang, R. Nurieva, Y. H. Wang, Y. Wang, L. Hood, Z. Zhu, Q. Tian, and C. Dong. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6: 1133-1141. (Pubitemid 41541791)
27. Nakae, S., Y. Iwakura, H. Suto, and S. J. Galli. 2007. Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17. J. Leukoc. Biol. 81: 1258-1268. (Pubitemid 46702045)
28. Ishigame, H., A. Nakajima, S. Saijo, Y. Komiyama, A. Nambu, T. Matsuki, S. Nakae, R. Horai, S. Kakuta, and Y. Iwakura. 2006. The role of TNFα and IL-17 in the development of excess IL-1 signaling-induced inflammatory diseases in IL-1 receptor antagonist-deficient mice. Ernst Schering Res. Found. Workshop 2006: 129-153.
29. Lubberts, E., L. A. Joosten, F. A. van de Loo, P. Schwarzenberger, J. Kolls, and W. B. van den Berg. 2002. Overexpression of IL-17 in the knee joint of collagen type II immunized mice promotes collagen arthritis and aggravates joint destruction. Inflamm. Res. 51: 102-104. (Pubitemid 34183634)
30. Lubberts, E., M. I. Koenders, B. Oppers-Walgreen, L. van den Bersselaar, C. J. Coenen-de Roo, L. A. Joosten, and W. B. van den Berg. 2004. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. 50: 650-659. (Pubitemid 38198849)
31. Nakae, S., A. Nambu, K. Sudo, and Y. Iwakura. 2003. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J. Immunol. 171: 6173-6177. (Pubitemid 37467240)
32. Komiyama, Y., S. Nakae, T. Matsuki, A. Nambu, H. Ishigame, S. Kakuta, K. Sudo, and Y. Iwakura. 2006. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J. Immunol. 177: 566-573. (Pubitemid 43939170)
33. Janeway, C. A., Jr., and R. Medzhitov. 1998. Introduction: the role of innate immunity in the adaptive immune response. Semin. Immunol. 10: 349-350. (Pubitemid 28499547)
34. He, R., M. K. Oyoshi, H. Jin, and R. S. Geha. 2007. Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge. Proc. Natl. Acad. Sci. USA 104: 15817-15822. (Pubitemid 350035382)
35. Park, H. S., M. Costalonga, R. L. Reinhardt, P. E. Dombek, M. K. Jenkins, and P. P. Cleary. 2004. Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection. Eur. J. Immunol. 34: 2843-2853. (Pubitemid 39430160)
36. 2, which inhibits generation of γ interferon-positive T cells. Infect. Immun. 76: 2651-2659.
37. Zhang, Z., T. B. Clarke, and J. N. Weiser. 2009. Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J. Clin. Invest. 119: 1899-1909.
38. Reis e Sousa, C. 2006. Dendritic cells in a mature age. Nat. Rev. Immunol. 6: 476-483.
39. Nakae, S., Y. Komiyama, A. Nambu, K. Sudo, M. Iwase, I. Homma, K. Sekikawa, M. Asano, and Y. Iwakura. 2002. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 17: 375-387. (Pubitemid 35279557)
40. Berlo, S. E., T. Guichelaar, C. B. Ten Brink, P. J. van Kooten, F. Hauet-Broeren, K. Ludanyi, W. van Eden, C. P. Broeren, and T. T. Glant. 2006. Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice. Arthritis Rheum. 54: 2423-2433. (Pubitemid 44205002)
41. Glant, T. T., G. Cs-Szabó, H. Nagase, J. J. Jacobs, and K. Mikecz. 1998. Progressive polyarthritis induced in BALB/c mice by aggrecan from normal and osteoarthritic human cartilage. Arthritis Rheum. 41: 1007-1018. (Pubitemid 28265403)
42. Glant, T. T., M. Radacs, G. Nagyeri, K. Olasz, A. Laszlo, F. Boldizsar, A. Hegyi, A. Finnegan, and K. Mikecz. 2011. Proteoglycan-induced arthritis and recombinant human proteoglycan aggrecan G1 domain-induced arthritis in BALB/c mice resembling two subtypes of rheumatoid arthritis. Arthritis Rheum. 63: 1312-1321.
43. Di Cesare, A., P. Di Meglio, and F. O. Nestle. 2009. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J. Invest. Dermatol. 129: 1339-1350.
44. Glant, T. T., A. Finnegan, and K. Mikecz. 2003. Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics. Crit. Rev. Immunol. 23: 199-250. (Pubitemid 37204432)
45. Stuart, J. M., A. S. Townes, and A. H. Kang. 1982. Nature and specificity of the immune response to collagen in type II collagen-induced arthritis in mice. J. Clin. Invest. 69: 673-683. (Pubitemid 12184965)
46. Inglis, J. J., G. Criado, M. Medghalchi, M. Andrews, A. Sandison, M. Feldmann, and R. O. Williams. 2007. Collagen-induced arthritis in C57BL/6 mice is associated with a robust and sustained T-cell response to type II collagen. Arthritis Res. Ther. 9: R113.
47. Ortmann, R. A., and E. M. Shevach. 2001. Susceptibility to collagen-induced arthritis: cytokine-mediated regulation. Clin. Immunol. 98: 109-118.
48. Constant, S. L., K. S. Lee, and K. Bottomly. 2000. Site of antigen delivery can influence T cell priming: pulmonary environment promotes preferential Th2-type differentiation. Eur. J. Immunol. 30: 840-847. (Pubitemid 30216257)
49. Jones, H. P., L. M. Hodge, K. Fujihashi, H. Kiyono, J. R. McGhee, and J. W. Simecka. 2001. The pulmonary environment promotes Th2 cell responses after nasal-pulmonary immunization with antigen alone, but Th1 responses are induced during instances of intense immune stimulation. J. Immunol. 167: 4518-4526. (Pubitemid 32954330)
50. Constant, S. L., J. L. Brogdon, D. A. Piggott, C. A. Herrick, I. Visintin, N. H. Ruddle, and K. Bottomly. 2002. Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ. J. Clin. Invest. 110: 1441-1448. (Pubitemid 35396915)
51. Zygmunt, B. M., F. Rharbaoui, L. Groebe, and C. A. Guzman. 2009. Intranasal immunization promotes th17 immune responses. J. Immunol. 183: 6933-6938.
52. + T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat. Immunol. 8: 369-377.
53. Aujla, S. J., Y. R. Chan, M. Zheng, M. Fei, D. J. Askew, D. A. Pociask, T. A. Reinhart, F. McAllister, J. Edeal, K. Gaus, et al. 2008. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med. 14: 275-281. (Pubitemid 351347908)
54. Luger, D., P. B. Silver, J. Tang, D. Cua, Z. Chen, Y. Iwakura, E. P. Bowman, N. M. Sgambellone, C. C. Chan, and R. R. Caspi. 2008. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J. Exp. Med. 205: 799-810. (Pubitemid 351549879)
55. Doodes, P. D., Y. Cao, K. M. Hamel, Y. Wang, R. L. Rodeghero, K. Mikecz, T. T. Glant, Y. Iwakura, and A. Finnegan. 2010. IFN-γ regulates the requirement for IL-17 in proteoglycan-induced arthritis. J. Immunol. 184: 1552-1559.
56. Denning, T. L., B. A. Norris, O. Medina-Contreras, S. Manicassamy, D. Geem, R. Madan, C. L. Karp, and B. Pulendran. 2011. Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization. J. Immunol. 187: 733-747.
57. Liu, C. H., Y. T. Fan, A. Dias, L. Esper, R. A. Corn, A. Bafica, F. S. Machado, and J. Aliberti. 2006. Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice. J. Immunol. 177: 31-35. (Pubitemid 43939111)
58. Zhan, Y., Y. Xu, S. Seah, J. L. Brady, E. M. Carrington, C. Cheers, B. A. Croker, L. Wu, J. A. Villadangos, and A. M. Lew. 2010. Resident and monocyte-derived dendritic cells become dominant IL-12 producers under different conditions and signaling pathways. J. Immunol. 185: 2125-2133.
59. Chen, J., B. P. Vistica, H. Takase, D. I. Ham, R. N. Fariss, E. F. Wawrousek, C. C. Chan, J. A. DeMartino, J. M. Farber, and I. Gery. 2004. A unique pattern of up- and down-regulation of chemokine receptor CXCR3 on inflammation-inducing Th1 cells. Eur. J. Immunol. 34: 2885-2894. (Pubitemid 39430164)
60. Hirota, K., H. Yoshitomi, M. Hashimoto, S. Maeda, S. Teradaira, N. Sugimoto, T. Yamaguchi, T. Nomura, H. Ito, T. Nakamura, et al. 2007. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J. Exp. Med. 204: 2803-2812. (Pubitemid 350179551)
61. Campbell, J. J., D. J. O'Connell, and M. A. Wurbel. 2007. Cutting edge: chemokine receptor CCR4 is necessary for antigen-driven cutaneous accumulation of CD4 T cells under physiological conditions. J. Immunol. 178: 3358-3362. (Pubitemid 46417598)
62. Freeman, C. M., V. R. Stolberg, B. C. Chiu, N. W. Lukacs, S. L. Kunkel, and S. W. Chensue. 2006. CCR4 participation in Th type 1 (mycobacterial) and Th type 2 (schistosomal) anamnestic pulmonary granulomatous responses. J. Immunol. 177: 4149-4158. (Pubitemid 44359950)
63. Andrew, D. P., N. Ruffing, C. H. Kim, W. Miao, H. Heath, Y. Li, K. Murphy, J. J. Campbell, E. C. Butcher, and L. Wu. 2001. C-C chemokine receptor 4 expression defines a major subset of circulating nonintestinal memory T cells of both Th1 and Th2 potential. J. Immunol. 166: 103-111. (Pubitemid 32038422)
64. Cua, D. J., and C. M. Tato. 2010. Innate IL-17-producing cells: the sentinels of the immune system. Nat. Rev. Immunol. 10: 479-489.
65. Roark, C. L., J. D. French, M. A. Taylor, A. M. Bendele, W. K. Born, and R. L. O'Brien. 2007. Exacerbation of collagen-induced arthritis by oligoclonal, IL-17-producing γδ T cells. J. Immunol. 179: 5576-5583.
66. + uveitogenic T cells. J. Immunol. 183: 560-567.
67. Sutton, C. E., S. J. Lalor, C. M. Sweeney, C. F. Brereton, E. C. Lavelle, and K. H. Mills. 2009. Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity 31: 331-341.
68. Dolhain, R. J., N. T. ter Haar, S. Hoefakker, P. P. Tak, M. de Ley, E. Claassen, F. C. Breedveld, and A. M. Miltenburg. 1996. Increased expression of interferon (IFN)-γ together with IFN-γ receptor in the rheumatoid synovial membrane compared with synovium of patients with osteoarthritis. Br. J. Rheumatol. 35: 24-32.
69. Steiner, G., M. Tohidast-Akrad, G. Witzmann, M. Vesely, A. Studnicka-Benke, A. Gal, M. Kunaver, P. Zenz, and J. S. Smolen. 1999. Cytokine production by synovial T cells in rheumatoid arthritis. Rheumatology (Oxford) 38: 202-213. (Pubitemid 29507155)
70. Cañete, J. D., S. E. Martínez, J. Farrés, R. Sanmartí, M. Blay, A. Gómez, G. Salvador, and J. Muñoz-Gómez. 2000. Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon γ is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies. Ann. Rheum. Dis. 59: 263-268. (Pubitemid 30305567)
71. Kim, K. W., M. L. Cho, M. K. Park, C. H. Yoon, S. H. Park, S. H. Lee, and H. Y. Kim. 2005. Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor κB-dependent pathway in patients with rheumatoid arthritis. Arthritis Res. Ther. 7: R139-R148.
72. Kotake, S., N. Udagawa, N. Takahashi, K. Matsuzaki, K. Itoh, S. Ishiyama, S. Saito, K. Inoue, N. Kamatani, M. T. Gillespie, et al. 1999. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J. Clin. Invest. 103: 1345-1352. (Pubitemid 29218305)
73. Ziolkowska, M., A. Koc, G. Luszczykiewicz, K. Ksiezopolska-Pietrzak, E. Klimczak, H. Chwalinska-Sadowska, and W. Maslinski. 2000. High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J. Immunol. 164: 2832-2838. (Pubitemid 30115519)
74. Yamada, H., Y. Nakashima, K. Okazaki, T. Mawatari, J. I. Fukushi, N. Kaibara, A. Hori, Y. Iwamoto, and Y. Yoshikai. 2008. Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann. Rheum. Dis.Dis. 67: 1299-1304.
75. Ito, Y., T. Usui, S. Kobayashi, M. Iguchi-Hashimoto, H. Ito, H. Yoshitomi, T. Nakamura, M. Shimizu, D. Kawabata, N. Yukawa, et al. 2009. γ/δ T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. Arthritis Rheum. 60: 2294-2303.
76. Church, L. D., A. D. Filer, E. Hidalgo, K. A. Howlett, A. M. Thomas, S. Rapecki, D. Scheel-Toellner, C. D. Buckley, and K. Raza. 2010. Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-α co-expression, but little interleukin-22 and interleukin-23R expression. Arthritis Res. Ther. 12: R184.
77. Raza, K., F. Falciani, S. J. Curnow, E. J. Ross, C. Y. Lee, A. N. Akbar, J. M. Lord, C. Gordon, C. D. Buckley, and M. Salmon. 2005. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res. Ther. 7: R784-R795.
78. Kirkham, B. W., M. N. Lassere, J. P. Edmonds, K. M. Juhasz, P. A. Bird, C. S. Lee, R. Shnier, and I. J. Portek. 2006. Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort). Arthritis Rheum. 54: 1122-1131. (Pubitemid 43672925)
79. Gullick, N. J., H. G. Evans, L. D. Church, D. M. Jayaraj, A. Filer, B. W. Kirkham, and L. S. Taams. 2010. Linking power Doppler ultrasound to the presence of th17 cells in the rheumatoid arthritis joint. PLoS ONE 5: e12516.
80. Zizzo, G., M. De Santis, S. L. Bosello, A. L. Fedele, G. Peluso, E. Gremese, B. Tolusso, and G. Ferraccioli. 2011. Synovial fluid-derived T helper 17 cells correlate with inflammatory activity in arthritis, irrespectively of diagnosis. Clin. Immunol. 138: 107-116.