T cells, B cells, and polarized immune response in the pathogenesis of fibrosis and systemic sclerosis

Current Opinion in Rheumatology

Volumn 20, Issue 6, 2008, Pages 707-712

  Chizzolini, Carlo ^a  

^a University Hospital and School of Medicine   (Switzerland)

Author keywords

B cells; Fibrosis; Scleroderma; T cells; Th2 cytokines; Vasculopathy

Indexed keywords

IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 13; INTERLEUKIN 4; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR;

ANTIGEN SPECIFICITY; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CLINICAL FEATURE; CYTOKINE PRODUCTION; DRUG MEGADOSE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; LUNG FIBROSIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SKIN FIBROSIS; SYSTEMIC SCLEROSIS; TH2 CELL;

ANIMALS; B-LYMPHOCYTES; CYTOKINES; DISEASE MODELS, ANIMAL; FIBROSIS; HUMANS; MODELS, IMMUNOLOGICAL; SCLERODERMA, SYSTEMIC; T-LYMPHOCYTES;

EID: 56249112642     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/BOR.0b013e32830c45ae     Document Type: Review

References (64)

1. Prescott RJ, Freemont AJ, Jones CJ, et al. Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol 1992; 166:255-263.
2. Chizzolini C. Update on pathophysiology of scleroderma with special reference to immunoinflammatory events. Ann Med 2007; 39:42-53.
3. Yurovsky VV, Wigley FM, Wise RA, White B. Skewing of the CD8+ T-cell repertoire in the lungs of patients with systemic sclerosis. Hum Immunol 1996; 48:84-97.
4. Sakkas LI, Xu B, Artlett CM, et al. Oligoclonal T cell expansion in the skin of patients with systemic sclerosis. J Immunol 2002; 168:3649-3659.
5. Farge D, Henegar C, Carmagnat M, et al. Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis Rheum 2005; 52:1555-1563.
6. Feghali-Bostwick CA, Tsai CG, Valentine VG, et al. Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. J Immunol 2007; 179:2592-2599. The first evidence that CD4+ T cells proliferate in the presence of an undefined lung antigen specifically present in IPF. It points to autoreactive process involved in IPF.
7. Hu PQ, Hurwitz AA, Oppenheim JJ. Immunization with DNA topoisomerase I induces autoimmune responses but not scleroderma-like pathologies in mice. J Rheumatol 2007; 34:2243-2252.
8. Hoffmann KF, McCarty TC, Segal DH, et al. Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions. FASEB J 2001; 15:2545-2547.
9. Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J Immunol 2003; 171:3655-3667.
10. Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 2004; 4:583-594.
11. Parel Y, Aurrand-Lions M, Scheja A, et al. Presence of CD4+CD8+ double-positive T cells with very high interleukin-4 production potential in lesional skin of patients with systemic sclerosis. Arthritis Rheum 2007; 56:3459-3467. Confirms that IL-4 producing T cells are present in SSc skin and identifies a novel T cell subset with distinctive characteristics and restricted TCR usage.
12. Atamas SP, Yurovsky VV, Wise R, et al. Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum 1999; 42:1168-1178.
13. Aliprantis AO, Wang J, Fathman JW, et al. Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Proc Natl Acad Sci U S A 2007; 104:2827-2830. Intriguing evidence indicating that T-bet, a master regulator of Th1 differentiation, is involved in IL-13 production by cells other than those of the adaptive immune system.
14. Fichtner-Feigl S, Strober W, Kawakami K, et al. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat Med 2006; 12:99-106.
15. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol 2008; 214:199-210.
16. Famularo G, Procopio A, Giacomelli R, et al. Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis. Clin Exp Immunol 1990; 81:368-372.
17. Needleman BW, Wigley FM, Stair RW. Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha, and interferon-gamma levels in sera from patients with scleroderma. Arthritis Rheum 1992; 35:67-72.
18. Salmon-Ehr V, Serpier H, Nawrocki B, et al. Expression of interleukin-4 in scleroderma skin specimens and scleroderma fibroblast cultures. Potential role in fibrosis. Arch Dermatol 1996; 132:802-806.
19. Mavalia C, Scaletti C, Romagnani P, et al. Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis. Am J Pathol 1997; 151:1751-1758.
20. Scaletti C, Vultaggio A, Bonifacio S, et al. Th2-oriented profile of male offspring T cells present in women with systemic sclerosis and reactive with maternal major histocompatibility complex antigens. Arthritis Rheum 2002; 46:445-450.
21. Ong C, Wong C, Roberts CR, et al. Anti-IL-4 treatment prevents dermal collagen deposition in the tight-skin mouse model of scleroderma. Eur J Immunol 1998; 28:2619-2629.
22. Kodera T, McGaha TL, Phelps R, et al. Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-beta production by fibroblasts. Proc Natl Acad Sci U S A 2002; 99:3800-3805.
23. Chiaramonte MG, Donaldson DD, Cheever AW, Wynn TA. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Invest 1999; 104:777-785.
24. Belperio JA, Dy M, Burdick MD, et al. Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 2002; 27:419-427.
25. Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999; 103:779-788.
26. Keane MP, Gomperts BN, Weigt S, et al. IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans syndrome. J Immunol 2007; 178:511-519.
27. Kolodsick JE, Toews GB, Jakubzick C, et al. Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts. J Immunol 2004; 172:4068-4076.
28. Fertin C, Nicolas JF, Gillery P, et al. Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell Mol Biol 1991; 37:823-829.
29. Chizzolini C, Parel Y, Scheja A, Dayer JM. Polarized subsets of human T-helper cells induce distinct patterns of chemokine production by normal and systemic sclerosis dermal fibroblasts. Arthritis Res Ther 2006; 8:R10.
30. Yamamoto T. Chemokines and chemokine receptors in scleroderma. Int Arch Allergy Immunol 2006; 140:345-356.
31. Strieter RM, Gomperts BN, Keane MP. The role of CXC chemokines in pulmonary fibrosis. J Clin Invest 2007; 117:549-556.
32. Boin F, De Fanis U, Bartlett SJ, et al. T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. Arthritis Rheum 2008; 58:1165-1174.
33. Luzina IG, Atamas SP, Wise R, et al. Gene expression in bronchoalveolar lavage cells from scleroderma patients. Am J Respir Cell Mol Biol 2002; 26:549-557.
34. Shimizu S, Yoshinouchi T, Niimi T, et al. Differing distributions of CXCR3- and CCR4-positive cells among types of interstitial pneumonia associated with collagen vascular diseases. Virchows Arch 2007; 450:51-58.
35. Del Galdo F, Jimenez SA. T cells expressing allograft inflammatory factor 1 display increased chemotaxis and induce a profibrotic phenotype in normal fibroblasts in vitro. Arthritis Rheum 2007; 56:3478-3488.
36. Askew D, Zhou L, Wu C, et al. Absence of cutaneous TNFalpha-producing CD4+ T cells and TNFalpha may allow for fibrosis rather than epithelial cytotoxicity in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. J Invest Dermatol 2007; 127:1905-1914. The role of TNF in fibrotic processes has generated a large debate, unresolved yet. This article supports the hypothesis that the lack of TNF is permissive for fibrosis development.
37. Zhou L, Askew D, Wu C, Gilliam AC. Cutaneous gene expression by DNA microarray in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. J Invest Dermatol 2007; 127:281-292.
38. Verrecchia F, Pessah M, Atfi A, Mauviel A. Tumor necrosis factor-alpha inhibits transforming growth factor-beta/Smad signaling in human dermal fibroblasts via AP-1 activation. J Biol Chem 2000; 275:30226-30231.
39. Chizzolini C, Parel Y, De Luca C, et al. Systemic sclerosis Th2 cells inhibit collagen production by dermal fibroblasts via membrane-associated tumor necrosis factor alpha. Arthritis Rheum 2003; 48:2593-2604.
40. Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000; 100:655-669.
41. Lakos G, Melichian D, Wu M, Varga J. Increased bleomycin-induced skin fibrosis in mice lacking the Th1-specific transcription factor T-bet. Pathobiology 2006; 73:224-237.
42. Wood N, Whitters MJ, Jacobson BA, et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2. J Exp Med 2003; 197:703-709.
43. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19:683-765.
44. Wilson MS, Elnekave E, Mentink-Kane MM, et al. IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. J Clin Invest 2007; 117:2941-2951. Identifies in vivo the complex interactions between profibrotic IL-13 and antifibrotic, anti-inflammatory IL-10 in lung disorder ultimately leading to fibrosis.
45. Whitfield ML, Finlay DR, Murray JI, et al. Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci U S A 2003; 100:12319-12324.
46. Lafyatis R, O'Hara C, Feghali-Bostwick CA, Matteson E. B cell infiltration in systemic sclerosis-associated interstitial lung disease. Arthritis Rheum 2007; 56:3167-3168.
47. Sato S, Hasegawa M, Fujimoto M, et al. Quantitative genetic variation in CD19 expression correlates with autoimmunity. J Immunol 2000; 165:6635-6643.
48. Yoshizaki A, Iwata Y, Komura K, et al. CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin-induced scleroderma. Am J Pathol 2008; 172:1650-1663. First evidence that members of pattern recognition receptors are involved in bleomycin-induced fibrosis and immunological abnormalities favoring B cell activation upon binding to an endogenous ligand. Example of an area of investigation focusing on invariant receptors and adaptive immunity.
49. Hasegawa M, Hamaguchi Y, Yanaba K, et al. B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis. Am J Pathol 2006; 169:954-966.
50. Matsushita T, Fujimoto M, Hasegawa M, et al. BAFF antagonist attenuates the development of skin fibrosis in tight-skin mice. J Invest Dermatol 2007; 127:2772-2780.
51. Matsushita T, Hasegawa M, Yanaba K, et al. Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes. Arthritis Rheum 2006; 54:192-201.
52. Komura K, Fujimoto M, Yanaba K, et al. Blockade of CD40/CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse. Ann Rheum Dis 2008; 67:867-872.
53. Nash RA, McSweeney PA, Crofford U, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007; 110:1388-1396.
54. Vonk MC, Marjanovic Z, van den Hoogen FH, et al. Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis. Ann Rheum Dis 2008; 67:98-104.
55. Fleming JN, Nash RA, McLeod DO, et al. Capillary regeneration in scleroderma: stem cell therapy reverses phenotype? PLoS ONE 2008; 3:e1452. First histological evidence that capillary loss in SSc can be reversed after high-dose immunosuppressive therapy and HSCT. It does not offer a mechanism for this phenomenon but suggests that components of the adaptive immune system may be involved in vasculopathy.
56. Daley E, Emson C, Guignabert C, et al. Pulmonary arterial remodeling induced by a Th2 immune response. J Exp Med 2008; 205:361-372. First in-vivo demonstration that T cells with Th2 function can lead to muscular hypertophic changes as observed in pulmonary artery hypertension. It opens the question whether fibrosis and vasculopathy in SSc have common roots.
57. Taraseviciene-Stewart L, Nicolls MR, Kraskauskas D, et al. Absence of T cells confers increased pulmonary arterial hypertension and vascular remodeling. Am J Respir Crit Care Med 2007; 175:1280-1289.
58. Iannone F, Riccardi MT, Guiducci S, et al. Bosentan regulates the expression of adhesion molecules on circulating T cells and serum soluble adhesion molecules in systemic sclerosis-associated pulmonary arterial hypertension. Ann Rheum Dis 2007. doi:10.1136/ard.2007.080424.
59. Matsushita Y, Hasegawa M, Matsushita T, et al. Intercellular adhesion molecule-1 deficiency attenuates the development of skin fibrosis in tight-skin mice. J Immunol 2007; 179:698-707.
60. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 2008; 28:454-467.
61. Kurasawa K, Hirose K, Sano H, et al. Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum 2000; 43:2455-2463.
62. Deleuran B, Abraham DJ. Possible implication of the effector CD4+ T-cell subpopulation TH17 in the pathogenesis of systemic scleroderma. Nat Clin Pract Rheumatol 2007; 3:682-683.
63. Hsu HC, Yang P, Wang J, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 2008; 9:166-175.
64. Yang L, Anderson DE, Baecher-Allan C, et al. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 2008. doi:10.1038/nature07021.