Skip to main content

Advertisement

Log in

Decreased PD-1 positive blood follicular helper T cells in patients with psoriasis

  • Concise Communication
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Follicular helper T (Tfh) cells are recently characterized subset of helper T cells, which are initially found in the germinal centers of B cell follicles. The major role of Tfh cells is helping B cell activation and antibody production during humoral immunity. Recently, blood Tfh cells were shown to be associated with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid and psoriasis. There is only one study which investigated Tfh cells in psoriasis patients. Therefore, in this study, we evaluated and analyzed blood Tfh cells in Korean patients with psoriasis. A total of 28 psoriasis patients and 16 healthy controls were enrolled. The frequency and absolute number of CXCR5+PD-1+ Tfh cells were decreased in patients with psoriasis compared to healthy controls. CD4+CXCR5+ T cells and CXCR5+ICOS+ Tfh cells did not show differences. The frequency and absolute number of CXCR5+PD-1+ Tfh cells in psoriasis patients negatively correlated with erythrocyte sedimentation rate and positively correlated with disease duration. The absolute number of CXCR5+ICOS+ Tfh cells also showed positive correlation with disease duration. However, the subpopulations of Tfh cells did not correlate with Psoriasis Area and Severity Index. Serum interleukin-21 level was significantly increased in psoriasis patients compared to healthy controls, however, its level did not correlate with clinical and experimental parameters of psoriasis patients. These findings suggest the decreased function of Tfh cells in psoriasis, which could result in attenuated B cell immune responses in the pathogenesis of psoriasis. However, further investigations are necessary to confirm the function of Tfh cells in psoriasis vulgaris.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Abbreviations

ASO:

Anti-streptolysin O

BCL-6:

B-cell lymphoma 6 protein

BP:

Bullous pemphigoid

BSA:

Body surface area

CCR:

CC chemokine receptors

CD:

Cluster of differentiation

CRP:

C-reactive protein

CXCR5:

C-X-C chemokine receptor type 5

ESR:

Erythrocyte sedimentation rate

ICOS:

Inducible T cell costimulator

IMIDs:

Immune-mediated inflammatory diseases

IL-21:

Interleukin-21

JDM:

Juvenile dermatomyositis

PASI:

Psoriasis Area and Severity Index

PBMC:

Peripheral blood mononuclear cells

PD-1:

Programmed cell death protein 1

SD:

Standard deviation

SLE:

Systemic lupus erythematosus

SS:

Sjögren’s syndrome

TFH:

Follicular helper T cell

References

  1. Ally MS, Prasad Hunasehally RY, Rodriguez-Justo M, Martin B, Verdolini R, Attard N, Child F, Attygalle A, Whittaker S, Morris S, Robson A (2013) Evaluation of follicular T-helper cells in primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma and dermatitis. J Cutan Pathol 40:1006–1013

    Article  PubMed  Google Scholar 

  2. Ambarus C, Yeremenko N, Tak PP, Baeten D (2012) Pathogenesis of spondyloarthritis: autoimmune or autoinflammatory? Curr Opin Rheumatol 24:351–358

    Article  CAS  PubMed  Google Scholar 

  3. Bautista-Caro MB, Arroyo-Villa I, Castillo-Gallego C, de Miguel E, Peiteado D, Plasencia-Rodriguez C, Villalba A, Sanchez-Mateos P, Puig-Kroger A, Martin-Mola E, Miranda-Carus ME (2014) Decreased frequencies of circulating follicular helper T cell counterparts and plasmablasts in ankylosing spondylitis patients Naive for TNF blockers. PLoS One 9:e107086

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bosisio FM, Cerroni L (2015) Expression of T-follicular helper markers in sequential biopsies of progressive mycosis fungoides and other primary cutaneous T-cell lymphomas. Am J Dermatopathol 37:115–121

    Article  PubMed  Google Scholar 

  5. Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, Forster R (2000) Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192:1545–1552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Buder K, Poppe LM, Brocker EB, Goebeler M, Rosenwald A, Geissinger E, Kerstan A (2013) Primary cutaneous follicular helper T-cell lymphoma: diagnostic pitfalls of this new lymphoma subtype. J Cutan Pathol 40:903–908

    PubMed  Google Scholar 

  7. Chang YS, Lee HT, Chen WS, Hsiao KH, Chen MH, Tsai CY, Chou CT (2012) Treatment of psoriasis with rituximab. J Am Acad Dermatol 66:e184–e185

    Article  PubMed  Google Scholar 

  8. Christophers E (2001) Psoriasis–epidemiology and clinical spectrum. Clin Exp Dermatol 26:314–320

    Article  CAS  PubMed  Google Scholar 

  9. Cohen JD (2008) Successful treatment of psoriatic arthritis with rituximab. Ann Rheum Dis 67:1647–1648

    Article  CAS  PubMed  Google Scholar 

  10. Craft JE (2012) Follicular helper T cells in immunity and systemic autoimmunity. Nat Rev Rheumatol 8:337–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Crotty S (2011) Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29:621–663

    Article  CAS  PubMed  Google Scholar 

  12. Crotty S (2014) T follicular helper cell differentiation, function, and roles in disease. Immunity 41:529–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gambichler T, Zhang Y, Hoxtermann S, Kreuter A (2013) Natural killer cells and B lymphocytes in peripheral blood of patients with psoriasis. Br J Dermatol 168:894–896

    Article  CAS  PubMed  Google Scholar 

  14. Gammon B, Guitart J (2012) Intertriginous mycosis fungoides: a distinct presentation of cutaneous T-cell lymphoma that may be caused by malignant follicular helper T cells. Arch Dermatol 148:1040–1044

    Article  PubMed  Google Scholar 

  15. Guidelli GM, Fioravanti A, Rubegni P, Feci L (2013) Induced psoriasis after rituximab therapy for rheumatoid arthritis: a case report and review of the literature. Rheumatol Int 33:2927–2930

    Article  CAS  PubMed  Google Scholar 

  16. Kanelleas A, Liapi C, Katoulis A, Stavropoulos P, Avgerinou G, Georgala S, Economopoulos T, Stavrianeas NG, Katsambas A (2011) The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept. Clin Exp Dermatol 36:845–850

    Article  CAS  PubMed  Google Scholar 

  17. Li Q, Liu Z, Dang E, Jin L, He Z, Yang L, Shi X, Wang G (2013) Follicular helper T Cells (Tfh) and IL-21 involvement in the pathogenesis of bullous pemphigoid. PLoS One 8:e68145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Locci M, Havenar-Daughton C, Landais E, Wu J, Kroenke MA, Arlehamn CL, Su LF, Cubas R, Davis MM, Sette A, Haddad EK, International AVIPCPI, Poignard P, Crotty S (2013) Human circulating PD-1+ CXCR3− CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity 39:758–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lowes MA, Suarez-Farinas M, Krueger JG (2014) Immunology of psoriasis. Annu Rev Immunol 32:227–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ma J, Zhu C, Ma B, Tian J, Baidoo SE, Mao C, Wu W, Chen J, Tong J, Yang M, Jiao Z, Xu H, Lu L, Wang S (2012) Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis. Clin Dev Immunol 2012:827480

    PubMed  PubMed Central  Google Scholar 

  21. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H (2011) Human blood CXCR5(+) CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34:108–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Niu J, Song Z, Yang X, Zhai Z, Zhong H, Hao F (2015) Increased circulating follicular helper T cells and activated B cells correlate with disease severity in patients with psoriasis. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.13027

    PubMed  Google Scholar 

  23. Park JH, Han JH, Kang HY, Lee ES, Kim YC (2014) Expression of follicular helper T-cell markers in primary cutaneous T-cell lymphoma. Am J Dermatopathol 36:465–470

    Article  PubMed  Google Scholar 

  24. Perera GK, Di Meglio P, Nestle FO (2012) Psoriasis. Annu Rev Pathol 7:385–422

    Article  CAS  PubMed  Google Scholar 

  25. Reveille JD (2012) Genetics of spondyloarthritis–beyond the MHC. Nat Rev Rheumatol 8:296–304

    Article  CAS  PubMed  Google Scholar 

  26. Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B (2000) CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192:1553–1562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schmitt N, Bentebibel SE, Ueno H (2014) Phenotype and functions of memory Tfh cells in human blood. Trends Immunol 35:436–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schmitt N, Ueno H (2013) Blood Tfh cells come with colors. Immunity 39:629–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Stolwijk C, Essers I, van Tubergen A, Boonen A, Bazelier MT, De Bruin ML, de Vries F (2014) The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study. Ann Rheum Dis. doi:10.1136/annrheumdis-2014-205253

    Google Scholar 

Download references

Acknowledgments

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI12C1672).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Min-Geol Lee.

Ethics declarations

Conflict of interest

None.

Additional information

D. Shin and D. Suk Kim contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shin, D., Kim, D.S., Kim, S.H. et al. Decreased PD-1 positive blood follicular helper T cells in patients with psoriasis. Arch Dermatol Res 308, 593–599 (2016). https://doi.org/10.1007/s00403-016-1679-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-016-1679-y

Keywords

Navigation