Skip to main content

Advertisement

SpringerLink
Log in

Th17 cells in systemic lupus erythematosus share functional features with Th17 cells from normal bone marrow and peripheral tissues

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

This study was designed to investigate the functional heterogeneity of human Th17 and how their plasticity shapes the nature of immune cell responses to inflammation and autoimmune diseases, such as systemic lupus erythematosus (SLE). We evaluated functional Th17 cell subsets based on the profile of cytokine production in peripheral blood (PB), bone marrow aspirates (BM) and lymph node biopsies (LN) from healthy individuals (n = 35) and PB from SLE patients (n = 34). Data were analysed by an automated method for merging and calculation of flow cytometric data, allowing us to identify eight Th17 subpopulations. Normal BM presented lower frequencies of Th17 (p = 0.006 and p = 0.05) and lower amount of IL-17 per cell (p = 0.03 and p = 0.02), compared to normal PB and LN biopsies. In the latter tissues were found increased proportions of Th17 producing TNF-α or TNF-α/IL-2 or IFN-γ/TNF-α/IL-2, while in BM, Th17 producing other cytokines than IL-17 was clearly decreased. In SLE patients, the frequency of Th17 was higher than in control, but the levels of IL-17 per cell were significantly reduced (p < 0.05). Among the eight generated subpopulations, despite the great functional heterogeneity of Th17 in SLE, a significant low proportion of Th17 producing TNF-α was found in inactive SLE, while active SLE showed a high proportion producing only IL-17. Our findings support the idea that the functional heterogeneity of Th17 cells could depend on the cytokine microenvironment, which is distinct in normal BM as well as in active SLE, probably due to a Th1/Th2 imbalance previously reported by our group.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Harrington LE, Mangan PR, Weaver CT (2006) Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol 18:349–356

    Article  PubMed  CAS  Google Scholar 

  2. Harrington LE, Hatton RD, Mangan PR et al (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132

    Article  PubMed  CAS  Google Scholar 

  3. Park H, Li Z, Yang XO et al (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 11:1133–1141

    Article  Google Scholar 

  4. Shi G, Cox CA, Vistica BP, Tan C, Wawrousek EF, Gery I (2008) Phenotype switching by inflammation-inducing polarized Th17 cells, but not by Th1 cells. J Immunol 181:7205–7213

    PubMed  CAS  Google Scholar 

  5. Lee YK, Turner H, Maynard CL et al (2009) Late developmental plasticity in the T helper 17 lineage. Immunity 30:92–107

    Article  PubMed  CAS  Google Scholar 

  6. Lexberg MH, Taubner A, Albrecht I et al (2010) IFN-γ and IL-12 synergize to convert in vivo generated Th17 into Th1/Th17 cells. Eur J Immunol 40:3017–3027

    Article  PubMed  CAS  Google Scholar 

  7. Yang XO et al (2008) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29:44–56

    Article  PubMed  CAS  Google Scholar 

  8. Walline CC, Kanakasabai S, Bright JJ (2011) IL-7Rα confers susceptibility to experimental autoimmune encephalomyelitis. Genes Immun 12:1–14

    Article  PubMed  CAS  Google Scholar 

  9. Miossec P (2003) Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy. Arthritis Rheum 48:594–601

    Article  PubMed  CAS  Google Scholar 

  10. RL Van bezooijen, Farih-Sips HC, Papapoulos SE, Lowik CW (1999) Interleukin-17: a new bone acting cytokine in vitro. J Bone Miner Res 14:1513–1521

    Article  Google Scholar 

  11. Shih DQ, Targan SR, McGovern D (2008) Recent advances in IBD pathogenesis: genetics and immunobiology. Curr Gastroenterol Rep 10:568–575

    Article  PubMed  Google Scholar 

  12. Kurasawa K, Hirose K, Sano H et al (2000) Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum 43:2455–2463

    Article  PubMed  CAS  Google Scholar 

  13. Crispin JC, Oukka M, Bayliss G et al (2008) Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol 181:8761–8766

    PubMed  CAS  Google Scholar 

  14. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW (2008) Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol 127:385–393

    Article  PubMed  CAS  Google Scholar 

  15. Dardalhon V, Korn T, Kuchroo VK, Anderson AC (2008) Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun 31:252–256

    Article  PubMed  CAS  Google Scholar 

  16. Annunziato F, Cosmi L, Santarlasci V et al (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204:1849–1861

    Article  PubMed  CAS  Google Scholar 

  17. Pedreira CE, Costa ES, Barrena S et al (2008) Generation of flow cytometry data files with a potentially infinite number of dimensions. EuroFlow Consortium. Cytometry A 73:834–846

    PubMed  Google Scholar 

  18. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  PubMed  CAS  Google Scholar 

  19. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  20. Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291

    PubMed  Google Scholar 

  21. Griffiths B, Mosca M, Gordon C (2005) Assessment of patients with systemic lupus erythematosus and the use of lupus disease activity indices. Best Pract Res Clin Rheumatol 19:685–708

    Article  PubMed  Google Scholar 

  22. Yang Y, Weiner J, Liu Y et al (2009) T-bet is essential for encephalitogenicity of both Th1 and Th17 cells. J Exp Med 206:1549–1564

    Article  PubMed  CAS  Google Scholar 

  23. Evans HG, Suddason T, Jackson I, Taams LS, Lord GM (2007) Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of toll-like receptor-activated monocytes. Proc Natl Acad Sci U S A 104:17034–17039

    Article  PubMed  CAS  Google Scholar 

  24. Garrett-Sinha LA, John S, Gaffen SL (2008) IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol 20:519–525

    Article  PubMed  CAS  Google Scholar 

  25. Mackenzie BS, Kastelein RA, Cua DJ (2006) Understanding the IL-23-IL-17 immune pathway. Trends Immunol 27:17–23

    Article  Google Scholar 

  26. Zhou L, Chong MM, Littman DR (2009) Plasticity of CD4+ T cell lineage differentiation. Immunity 30:646–655

    Article  PubMed  CAS  Google Scholar 

  27. Shen F, Gaffen SL (2008) Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy. Cytokine 41:92–104

    Article  PubMed  CAS  Google Scholar 

  28. Henriques A, Inês L, Couto M et al (2010) Frequency and functional activity of Th17, Tc17 and other T cell subsets in systemic lupus erythematosus. Cell Immunol 264:97–103

    Article  PubMed  CAS  Google Scholar 

  29. Ermann J, Bermas BL (2007) The biology behind the new therapies for SLE. Int J Clin Pract 61:2113–2119

    Article  PubMed  CAS  Google Scholar 

  30. Ramirez F, Fowell DJ, Puklavec M, Simmonds S, Mason D (1996) Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro. J Immunol 156:2406–2412

    PubMed  CAS  Google Scholar 

  31. Akahoshi M, Nakashima H, Tanaka Y et al (1999) Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus. Arthritis Rheum 42:1644–1648

    Article  PubMed  CAS  Google Scholar 

  32. Chen S, Hu D, Shi X, Shen N, Gu Y, Bao C (2000) The relationship between Th1/Th2-type cells and disease activity in patients with systemic lupus erythematosus. Chin Med J 113:877–880

    PubMed  CAS  Google Scholar 

Download references

Disclosures

None.

Author information

Authors and Affiliations

  1. Cytometry Service of the Histocompatibility Center of Coimbra, Portugal, Histocompatibility Center of Coimbra, Edifício São Jerónimo, 4º Piso, Praceta Mota Pinto, 3001-301, Coimbra, Portugal

    Ana Henriques, Maria Luísa Pais & Artur Augusto Paiva

  2. Rheumatology Service of the University Hospitals of Coimbra, Portugal, Avenida Bissaya Barreto, 3000-075, Coimbra, Portugal

    Luís Inês & José António Pereira da Silva

  3. Rheumatology Service of the University Hospitals of Coimbra, Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal

    Luís Inês

Authors
  1. Ana Henriques
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luís Inês
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Luísa Pais
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José António Pereira da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Artur Augusto Paiva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Artur Augusto Paiva.

Additional information

Ana Henriques and Luís Inês contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henriques, A., Inês, L., Pais, M.L. et al. Th17 cells in systemic lupus erythematosus share functional features with Th17 cells from normal bone marrow and peripheral tissues. Clin Rheumatol 31, 483–491 (2012). https://doi.org/10.1007/s10067-011-1860-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-011-1860-9

Keywords

Search

Navigation