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Disruption of Circulating CD4+ T-Lymphocyte Subpopulations in Psoriasis Patients is Ameliorated by Narrow-Band UVB Therapy

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Abstract

Narrow-band UVB (NB-UVB) therapy is widely used in the treatment of psoriasis; however, its precise mechanism is still unclear. To investigate the circulating CD4+ T-lymphocyte subpopulations in psoriasis patients before and after NB-UVB, thus providing new insights into the mechanism of NB-UVB in the treatment of psoriasis. We performed NB-UVB treatments for psoriasis patients (n = 30) and used flow cytometry, real-time PCR, and ELISA for the detection of circulating CD4+ T-lymphocyte subpopulations. The results were compared with healthy controls (n = 20) as well. We found increased circulating T helper 1 (Th1) and Th17 cell levels as well as decreased circulating regulatory T cells (Treg) levels compared to healthy controls. Additionally, there was a positive correlation between the percentage of circulating Th17 cells and Psoriasis Area and Severity Index (PASI) score. Furthermore, the percentage of circulating Th17 cells was negatively correlated with the Treg cells which led to an imbalance of Th17/Treg. NB-UVB therapy significantly reduced circulating Th1and Th17 cell levels while increasing Treg cell levels. These findings indicate that the overexpression of Th1 and Th17 cells together with the imbalance of Th17/Treg cells may play an important role in the pathogenesis of psoriasis. The mechanism of NB-UVB in the treatment of psoriasis may be through the inhibition of Th1 and Th17 cell immune response as well as the promotion of Treg cell immune response, thus ameliorating the disorder of circulating CD4+ T-lymphocyte subsets.

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References

  1. Gulletta, E., Bottoni, U., & Foti, D. P. (2013). Psoriasis, a new challenge for laboratory medicine. Clinical Chemistry and Laboratory Medicine: CCLM/FESCC, 51, 1363–1368.

    Article  CAS  Google Scholar 

  2. Mendoza, L. (2013). A virtual culture of CD4+ T lymphocytes. Bulletin of Mathematical Biology, 75, 1012–1029.

    Article  PubMed  Google Scholar 

  3. Romagnani, S. (2000). T-cell subsets (Th1 versus Th2). Annals of allergy, Asthma & Immunology: Official Publication of the American College of Allergy, Asthma, & Immunology, 85, 9–18; quiz 18, 21.

  4. Kidd, P. (2003). Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Alternative Medicine Review: A Journal of Clinical Therapeutic, 8, 223–246.

    Google Scholar 

  5. Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., et al. (2005). Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunology, 6, 1123–1132.

    Article  CAS  PubMed  Google Scholar 

  6. Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y. H., et al. (2005). A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature Immunology, 6, 1133–1141.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Fouser, L. A., Wright, J. F., Dunussi-Joannopoulos, K., & Collins, M. (2008). Th17 cytokines and their emerging roles in inflammation and autoimmunity. Immunological Reviews, 226, 87–102.

    Article  CAS  PubMed  Google Scholar 

  8. Kagami, S., Rizzo, H. L., Lee, J. J., Koguchi, Y., & Blauvelt, A. (2010). Circulating Th17, Th22, and Th1 cells are increased in psoriasis. The Journal of Investigative Dermatology, 130, 1373–1383.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Lowes, M. A., Kikuchi, T., Fuentes-Duculan, J., Cardinale, I., Zaba, L. C., Haider, A. S., et al. (2008). Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. The Journal of Investigative Dermatology, 128, 1207–1211.

    Article  CAS  PubMed  Google Scholar 

  10. Johansen, C., Usher, P. A., Kjellerup, R. B., Lundsgaard, D., Iversen, L., & Kragballe, K. (2009). Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. The British Journal of Dermatology, 160, 319–324.

    Article  CAS  PubMed  Google Scholar 

  11. Miyara, M., & Sakaguchi, S. (2007). Natural regulatory T cells: Mechanisms of suppression. Trends in Molecular Medicine, 13, 108–116.

    Article  CAS  PubMed  Google Scholar 

  12. Ohkura, N., Kitagawa, Y., & Sakaguchi, S. (2013). Development and maintenance of regulatory T cells. Immunity, 38, 414–423.

    Article  CAS  PubMed  Google Scholar 

  13. Noack, M., & Miossec, P. (2014). Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmunity Reviews, 13, 668–677.

  14. Cai, Y., Fleming, C., & Yan, J. (2012). New insights of T cells in the pathogenesis of psoriasis. Cellular & Molecular Immunology, 9, 302–309.

    Article  CAS  Google Scholar 

  15. Ozawa, M., Ferenczi, K., Kikuchi, T., Cardinale, I., Austin, L. M., Coven, T. R., et al. (1999). 312-nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cells within psoriatic lesions. The Journal of Experimental Medicine, 189, 711–718.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Hamakawa, M., Sugihara, A., Okamoto, H., & Horio, T. (2006). Ultraviolet B radiation suppresses Langerhans cell migration in the dermis by down-regulation of alpha4 integrin. Photodermatology, Photoimmunology and Photomedicine, 22, 116–123.

    Article  CAS  PubMed  Google Scholar 

  17. Piskin, G., Tursen, U., Sylva-Steenland, R. M., Bos, J. D., & Teunissen, M. B. (2004). Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a decrease in the expression of IFN-gamma inducers—IL-12, IL-18 and IL-23. Experimental Dermatology, 13, 764–772.

    Article  CAS  PubMed  Google Scholar 

  18. Sigmundsdottir, H., Johnston, A., Gudjonsson, J. E., & Valdimarsson, H. (2005). Narrowband-UVB irradiation decreases the production of pro-inflammatory cytokines by stimulated T cells. Archives of Dermatological Research, 297, 39–42.

    Article  CAS  PubMed  Google Scholar 

  19. Walters, I. B., Ozawa, M., Cardinale, I., Gilleaudeau, P., Trepicchio, W. L., Bliss, J., et al. (2003). Narrowband (312-nm) UV-B suppresses interferon gamma and interleukin (IL) 12 and increases IL-4 transcripts: Differential regulation of cytokines at the single-cell level. Archives of Dermatology, 139, 155–161.

    Article  CAS  PubMed  Google Scholar 

  20. Racz, E., Prens, E. P., Kurek, D., Kant, M., de Ridder, D., Mourits, S., et al. (2011). Effective treatment of psoriasis with narrow-band UVB phototherapy is linked to suppression of the IFN and Th17 pathways. The Journal of Investigative Dermatology, 131, 1547–1558.

    Article  CAS  PubMed  Google Scholar 

  21. Johnson-Huang, L. M., Suarez-Farinas, M., Sullivan-Whalen, M., Gilleaudeau, P., Krueger, J. G., & Lowes, M. A. (2010). Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. The Journal of Investigative Dermatology, 130, 2654–2663.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Piskin, G., Koomen, C. W., Picavet, D., Bos, J. D., & Teunissen, M. B. (2003). Ultraviolet-B irradiation decreases IFN-gamma and increases IL-4 expression in psoriatic lesional skin in situ and in cultured dermal T cells derived from these lesions. Experimental Dermatology, 12, 172–180.

    Article  CAS  PubMed  Google Scholar 

  23. Shi, X., Jin, L., Dang, E., Chang, T., Feng, Z., Liu, Y., et al. (2011). IL-17A upregulates keratin 17 expression in keratinocytes through STAT1- and STAT3-dependent mechanisms. The Journal of Investigative Dermatology, 131, 2401–2408.

    Article  CAS  PubMed  Google Scholar 

  24. Jin, L., & Wang, G. (2014). Keratin 17: A Critical Player in the Pathogenesis of Psoriasis. Medicinal Research Reviews, 34, 438–454.

  25. Chan, J. R., Blumenschein, W., Murphy, E., Diveu, C., Wiekowski, M., Abbondanzo, S., et al. (2006). IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. The Journal of Experimental Medicine, 203, 2577–2587.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Zhang, L., Yang, X. Q., Cheng, J., Hui, R. S., & Gao, T. W. (2010). Increased Th17 cells are accompanied by FoxP3(+) Treg cell accumulation and correlated with psoriasis disease severity. Clinical immunology, 135, 108–117.

    Article  CAS  PubMed  Google Scholar 

  27. Kondelkova, K., Vokurkova, D., Krejsek, J., Borska, L., Fiala, Z., Hamakova, K., et al. (2012). The number of immunoregulatory T cells is increased in patients with psoriasis after Goeckerman therapy. Acta medica, 55, 91–95.

    CAS  PubMed  Google Scholar 

  28. Yun, W. J., Lee, D. W., Chang, S. E., Yoon, G. S., Huh, J. R., Won, C. H., et al. (2010). Role of CD4CD25FOXP3 regulatory T cells in psoriasis. Annals of Dermatology, 22, 397–403.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Bovenschen, H. J., van de Kerkhof, P. C., van Erp, P. E., Woestenenk, R., Joosten, I., & Koenen, H. J. (2011). Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin. The Journal of Investigative Dermatology, 131, 1853–1860.

    Article  CAS  PubMed  Google Scholar 

  30. Singh, K., Gatzka, M., Peters, T., Borkner, L., Hainzl, A., Wang, H., et al. (2013). Reduced CD18 levels drive regulatory T cell conversion into Th17 cells in the CD18hypo PL/J mouse model of psoriasis. The Journal of Immunology, 190, 2544–2553.

    Article  CAS  PubMed  Google Scholar 

  31. Brazzelli, V., Barbagallo, T., Trevisan, V., Muzio, F., De Silvestri, A., & Borroni, G. (2008). The duration of clinical remission of photochemotherapy and narrow-band UV-B phototherapy in the treatment of psoriasis: A retrospective study. International Journal of Immunopathology and Pharmacology, 21, 481–484.

    CAS  PubMed  Google Scholar 

  32. Furuhashi, T., Saito, C., Torii, K., Nishida, E., Yamazaki, S., & Morita, A. (2013). Photo(chemo)therapy reduces circulating Th17 cells and restores circulating regulatory T cells in psoriasis. PLoS ONE, 8, e54895.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Elghandour, T. M., Youssef Sel, S., Aly, D. G., Abd Elhameed, M. S., & Abdel Moneim, M. M. (2013). Effect of narrow band ultraviolet B therapy versus methotrexate on serum levels of interleukin-17 and interleukin-23 in Egyptian patients with severe psoriasis. Dermatology Research and Practice, 2013, 618269.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Eysteinsdottir, J. H., Sigurgeirsson, B., Olafsson, J. H., Fridriksson, T., Agnarsson, B. A., Daviethsson, S., et al. (2013). The role of Th17/Tc17 peripheral blood T cells in psoriasis and their positive therapeutic response. Scandinavian Journal of Immunology, 78, 529–537.

    Article  CAS  PubMed  Google Scholar 

  35. Li, J., Hou, R., Yang, Y., Liu, R., Zhao, X., Li, X., et al. (2013). Narrowband ultraviolet B interferes with gene expression in the peripheral blood T cells of patients with psoriasis. Dermatology, 226, 128–137.

    Article  CAS  PubMed  Google Scholar 

  36. Ekman, A. K., Sigurdardottir, G., Carlstrom, M., Kartul, N., Jenmalm, M. C., & Enerback, C. (2013). Systemically elevated Th1-, Th2- and Th17-associated chemokines in psoriasis vulgaris before and after ultraviolet B treatment. Acta Dermato-Venereologica, 93, 527–531.

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank all members from the Department of Dermatology of Shanghai Tenth People’s Hospital for their advice and encouragement. We thank Andrew Armbruster for his editorial assistance. This work was supported in part by grants from National Science Foundation of China (81301356) (81360236), National Science Foundation of Shanghai (13ZR1432200), and the Science and Technology Commission of Shanghai Municipality Grant (134119b0700).

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Authors and Affiliations

  1. Department of Dermatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China

    Xiuxiu Wang, Yu Gong, Junying Gu, Wenjuan Chen & Yuling Shi

  2. Department of Gynaecology and Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China

    Guanghua Wang

  3. Department of Dermatopathology, Shanghai Skin Disease Hospital, Shanghai, 200443, China

    Yeqiang Liu

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  1. Xiuxiu Wang
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  2. Guanghua Wang
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  7. Yuling Shi
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Correspondence to Yuling Shi.

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Xiuxiu Wang and Guanghua Wang have contributed equally to this study.

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Wang, X., Wang, G., Gong, Y. et al. Disruption of Circulating CD4+ T-Lymphocyte Subpopulations in Psoriasis Patients is Ameliorated by Narrow-Band UVB Therapy. Cell Biochem Biophys 71, 499–507 (2015). https://doi.org/10.1007/s12013-014-0230-z

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  • DOI: https://doi.org/10.1007/s12013-014-0230-z

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