Imbalance of Peripheral Blood T Helper Type 17 Responses in Patients with Vitiligo
Abstract
There is growing evidence to suggest that Th cells play pivotal roles in a variety of chronic inflammatory diseases, including vitiligo. However, the exact role of different subsets of Th cells in the pathogenesis of vitiligo is still a question. The purpose of present study was to determine the mRNA expression level of Th17 master transcription factor retinoic acid receptor-related orphan receptors gamma (RORɣt) and cytokine mRNA and protein expression profiles of Th17 cells. 22 patients with vitiligo and 22 normal subjects were enrolled in the study. Gene expression profiles of freshly isolated peripheral blood mononuclear cells (PBMCs) were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). Plasma concentrations of IL-17A and IL-22 were also assayed using ELISA kits. The results showed that RORɣt, IL-17A and IL-22 mRNA expression were increased in patients remarkably compared to healthy controls (p<0.05). Furthermore, plasma IL-17A and IL-22 levels were also higher in vitiligo patients versus controls (p<0.001). These data suggest that a deregulated Th17 adaptive immune response may contribute to the pathogenesis of vitiligo.
1. Rashighi M, Harris JE. Vitiligo Pathogenesis and Emerging Treatments. Dermatol Clin 2017; 35(2):257-65.
2. Richmond JM, Frisoli ML, Harris JE. Innate immune mechanisms in vitiligo: danger from within. Curr Opin Immunol 2013; 25(6):676-82.
3. Glassman SJ. Vitiligo, Reactive oxygen species and T-cells. Clin Sci (Lond) 2011; 120(3):99-120.
4. Sandoval-Cruz M, García-Carrasco M, Sánchez-Porras R, Mendoza-Pinto C, Jiménez-Hernández M, Munguía-Realpozo P, et al. Immunopathogenesis of vitiligo. Autoimmun Rev 2011; 10(12):762-5.
5. Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol 2016; 28(4):163-71.
6. Wilke CM, Bishop K, Fox D, Zou W. Deciphering the role of Th17 cells in human disease. Trends Immunol 2011; 32(12):603-11.
7. Singh SP, Zhang HH, Foley JF, Hedrick MN, Farber JM. Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J Immunol 2008; 180(1):214-21.
8. Bassiouny DA, Shaker O. Role of interleukin-17 in the pathogenesis of vitiligo. Clin Exp Dermatol 2011; 36(3):292-7.
9. Wang CQ, Cruz-Inigo AE, Fuentes-Duculan J, Moussai D, Gulati N, Sullivan-Whalen M, et al. Th17 cells and activated dendritic cells are increased in vitiligo lesions. PLoS One 2011; 6(4):e18907.
10. Shi F, Erf GF. IFN-γ, IL-21, and IL-10 co-expression in evolving autoimmune vitiligo lesions of Smyth line chickens. J Invest Dermatol 2012; 132(3 Pt 1):642-9.
11. Nouri-Koupaee A, Mansouri P, Jahanbini H, Sanati MH, Jadali Z. Differential expression of mRNA for T-bet and GATA-3 transcription factors in peripheral blood mononuclear cells of patients with vitiligo. Clin Exp Dermatol 2015; 40(7):735-40.
12. Dos Passos GR, Sato DK, Becker J, Fujihara K. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications. Mediators Inflamm 2016; 2016:5314541.
13. Krueger GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, Wang Y, et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 2007; 356(6):580-92.
14. Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, et al. IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 2009; 123(6):1244-52.
15. Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 2008; 8(5): 337-348.
16. Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature 2008; 453(7198):1051-7.
17. Kotobuki Y, Tanemura A, Yang L, Itoi S, Wataya-Kaneda M, Murota H, et al. Dysregulation of melanocyte function by Th17-related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris. Pigment Cell Melanoma Res 2012; 25(2):219-30.
18. Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 2008; 58(8):2307-17.
19. Zhou L, Shi YL, Li K, Hamzavi I, Gao TW, Huggins RH, et al. Increased circulating Th17 cells and elevated serum levels of TGF-beta and IL-21 are correlated with human non-segmental vitiligo development. Pigment Cell Melanoma Res 2015; 28(3):324-9.
20. Elela MA, Hegazy RA, Fawzy MM, Rashed LA, Rasheed H. Interleukin 17, interleukin 22 and FoxP3 expression in tissue and serum of non-segmental vitiligo: a case- controlled study on eighty-four patients. Eur J Dermatol 2013; 23(3):350-5.
21. Basak PY, Adiloglu AK, Ceyhan AM, Tas T, Akkaya VB. The role of helper and regulatory T cells in the pathogenesis of vitiligo. J Am Acad Dermatol 2009; 60(2):256-60.
22. Hegazy RA, Fawzy MM, Gawdat HI, Samir N, Rashed LA. T helper 17 and Tregs: a novel proposed mechanism for NB-UVB in vitiligo. Exp Dermatol 2014; 23(4):283-6.
23. Tanemura A, Kotobuki Y, Itoi S, Takata T, Sano S, Katayama I. Positive link between STAT3 activation and Th17 cell infiltration to the lesional skin in vitiligo vulgaris. J Dermatol Sci 2012; 67(3):207-9.
24. Kolls JK, Lindén A. Interleukin-17 family members and inflammation. Immunity 2004; 21(4):467-76.
25. Diveu C, McGeachy MJ, Cua DJ. Cytokines that regulate autoimmunity. Curr Opin Immunol 2008; 20(6):663-8.
26. Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabiani M,et al. New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 2002; 15(2):87-92.
27. Moretti S, Fabbri P, Baroni G, Berti S, Bani D, Berti E, et al. Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis. Histol Histopathol 2009; 24(7):849-57.
28. Kotobuki Y, Tanemura A, Yang L, Itoi S, Wataya-Kaneda M, Murota H, et al. Dysregulation of melanocyte function by Th17-related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris. Pigment Cell Melanoma Res 2012; 25(2):219-30.
29. Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 2009; 31(5):787-98.
30. van den Boorn JG, Konijnenberg D, Dellemijn TA, van der Veen JP, Bos JD, Melief CJ, et al. Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 2009; 129(9):2220-32.
31. Zhang BX, Lin M, Qi XY, Zhang RX, Wei ZD, Zhu J, et al. Characterization of circulating CD8+T cells expressing skin homing and cytotoxic molecules in active non-segmental vitiligo. Eur J Dermatol 2013; 23(3):331-8.
32. Griffin GK, Newton G, Tarrio ML, Bu DX, Maganto-Garcia E, Azcutia V, et al. IL-17 and TNF-α sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation. J Immunol 2012; 188(12):6287-99.
33. Schröder JM, Gregory H, Young J, Christophers E. Neutrophil-activating proteins in psoriasis. J Invest Dermatol 1992; 98(2):241-7.
34. Le Poole IC, van den Wijngaard RM, Westerhof W, Das PK. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol 1996; 148(4):1219-28.
35. Gliński W, Barszcz D, Janczura E, Zarebska Z, Jabłońska S. Neutral proteinases and other neutrophil enzymes in psoriasis, and their relation to disease activity. Br J Dermatol 1984; 111(2):147-54.
36. Di Dalmazi G, Hirshberg J, Lyle D, Freij JB, Caturegli P. Reactive oxygen species in organ-specific autoimmunity. Auto Immun Highlights 2016; 7(1):11.
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Issue | Vol 17, No 2 (2018) | |
Section | Original Article(s) | |
Keywords | ||
Autoimmunity Cytokines Gene expression profiling T lymphocyte Vitiligo |
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