Skip to main content

Advertisement

Log in

Expression profiles of Th17 pathway related genes in human systemic lupus erythematosus

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Recently, evidence is emerging that inappropriate regulation of type 17 T helper cells (Th17) plays a fundamental role in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). However, the role of Th17-related cytokines in SLE remains elusive. To further investigate the role and imbalance of Th17-related cytokines in the pathogenesis of SLE. A Quantitative RT-PCR Array (Human Th17 for Autoimmunity & Inflammation PCR Array) analyses were performed to study Th17-related genes expression in peripheral white blood cells of 25 new-onset patients with SLE and 15 healthy subjects. When gene expression for SLE patients was compared to the mean of normal controls, among the 84 target genes related to Th17 pathway, 7 (CXCL1, ICAM1, IL10, IL5, IL8, ISG20, JAK2,) were upregulated and 6 (CD28, CD40LG, S1PR1, IL17RE, IL23R, RORC) downregulated. However, comparisons of mRNA expression of Th17 related cytokines between lupus nephritis (LN) patients and SLE patients without nephritis (SLE non LN) showed no significant difference. In conclusion, SLE patients and normal controls showed different expression of a few genes in Th17 pathway, indicating that the pathway may be involved in the pathogenesis of SLE.

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.

Fig. 1

Similar content being viewed by others

References

  1. Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939

    Article  PubMed  CAS  Google Scholar 

  2. Goodnow CC, Sprent J, de St Groth BF et al (2005) Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435:590–597

    Article  PubMed  CAS  Google Scholar 

  3. Shlomchik MJ, Craft JE, Mamula MJ (2001) From T to B and back again: positive feedback in systemic autoimmune disease. Nat Rev Immunol 1:147–153

    Article  PubMed  CAS  Google Scholar 

  4. Tsokos GC, Mitchell JP, Juang Y-T (2003) T cell abnormalities in human and mouse lupus: intrinsic and extrinsic. Curr Opin Rheumatol 15:542–547

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Nalbandian A, Crispín JC, Tsokos GC (2009) Interleukin-17 and systemic lupus erythematosus: current concepts. Clin Exp Immunol 157:209–215

    Article  PubMed  CAS  Google Scholar 

  7. 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 

  8. Wong CK, Ho CY, Li EK et al (2000) Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus 9:589–593

    Article  PubMed  CAS  Google Scholar 

  9. Wong CK, Lit LC, Tam LS et al (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 

  10. Zhao XF, Pan HF, Yuan H et al (2010) Increased serum interleukin 17 in patients with systemic lupus erythematosus. Mol Biol Rep 37:81–85

    Article  PubMed  Google Scholar 

  11. Kwan BC, Tam LS, Lai KB et al (2009) The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus. Rheumatology (Oxford) 48:1491–1497

    Article  CAS  Google Scholar 

  12. Crispín 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  Google Scholar 

  13. Wang Y, Ito S, Chino Y et al (2009) Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis. Clin Exp Immunol 159:1–10

    Article  PubMed  Google Scholar 

  14. Kang HK, Liu M, Datta SK et al (2007) Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of inflammatory Th17 cells. J Immunol 178:7849–7858

    PubMed  CAS  Google Scholar 

  15. Wu HY, Quintana FJ, Weiner HL (2008) Nasal anti-CD3 antibody ameliorates lupus by inducing an IL-10-secreting CD4+CD25-LAP+ regulatory T cell and is associated with down-regulation of IL-17+CD4+ICOS+CXCR5+ follicular helper T cells. J Immunol 181:6038–6050

    PubMed  CAS  Google Scholar 

  16. Pan HF, Ye DQ, Li XP (2008) Type 17 T-helper cells might be a promising therapeutic target for systemic lupus erythematosus. Nat Clin Pract Rheumatol 4:352–353

    PubMed  CAS  Google Scholar 

  17. 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 

  18. Pan HF, Zhao XF, Yuan H et al (2009) Decreased serum IL-22 levels in patients with systemic lupus erythematosus. Clin Chim Acta 401:179–180

    Article  PubMed  CAS  Google Scholar 

  19. Cheng F, Guo Z, Xu H et al (2009) Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis 68:604–606

    Article  PubMed  CAS  Google Scholar 

  20. Furuse S, Fujii H, Kaburagi Y et al (2003) Serum concentrations of the CXC chemokines interleukin 8 and growth-regulated oncogene-alpha are elevated in patients with systemic sclerosis. J Rheumatol 30:1524–1528

    PubMed  CAS  Google Scholar 

  21. van de Stolpe A, van der Saag PT (1996) Intercellular adhesion molecule-1. J Mol Med 74:13–33

    Article  PubMed  Google Scholar 

  22. Kim K, Brown EE, Choi CB et al (2012) Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries. Ann Rheum Dis. doi:10.1136/annrheumdis-2011-201100

    Google Scholar 

  23. López P, Gutiérrez C, Suárez A (2010) IL-10 and TNFalpha genotypes in SLE. J Biomed Biotechnol 2010:838390

    Article  PubMed  Google Scholar 

  24. Elwakkad AS, Said RN, Muhammad SI et al (2007) Role for leptin and prolactin in human juvenile rheumatic diseases. Pak J Biol Sci 10:1984–1989

    Article  PubMed  CAS  Google Scholar 

  25. Holcombe RF, Baethge BA, Wolf RE et al (1994) Correlation of serum interleukin-8 and cell surface lysosome-associated membrane protein expression with clinical disease activity in systemic lupus erythematosus. Lupus 3:97–102

    Article  PubMed  CAS  Google Scholar 

  26. Hrycek E, Franek A, Błaszczak E et al (2012) Serum levels of selected chemokines in systemic lupus erythematosus patients. Rheumatol Int. doi:10.1007/s00296-012-2393-5

    Google Scholar 

  27. Rovin BH, Lu L, Zhang X (2002) A novel interleukin-8 polymorphism is associated with severe systemic lupus erythematosus nephritis. Kidney Int 62:261–265

    Article  PubMed  CAS  Google Scholar 

  28. Horio T, Murai M, Inoue T et al (2004) Crystal structure of human ISG20, an interferon-induced antiviral ribonuclease. FEBS Lett 577:111–116

    Article  PubMed  CAS  Google Scholar 

  29. Ishii T, Onda H, Tanigawa A et al (2005) Isolation and expression profiling of genes upregulated in the peripheral blood cells of systemic lupus erythematosus patients. DNA Res 12:429–439

    Article  PubMed  CAS  Google Scholar 

  30. Lu LD, Stump KL, Wallace NH et al (2011) Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice using CEP-33779, a novel, orally active, selective inhibitor of JAK2. J Immunol 187:3840–3853

    Article  PubMed  CAS  Google Scholar 

  31. Wong CK, Lit LCW, Tam LS et al (2005) Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus. Rheumatology 44:989–994

    Article  PubMed  CAS  Google Scholar 

  32. Hebbar M, Jeannin P, Magistrelli G et al (2004) Detection of circulating soluble CD28 in patients with lupus erythematosus, primary Sjögren syndrome and systemic sclerosis. Clin Exp Immunol 136:388–392

    Article  PubMed  CAS  Google Scholar 

  33. Brambila-Tapia AJ, Gámez-Nava JI, Salazar-Páramo M et al (2011) Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus. Rheumatol Int 31:1321–1324

    Article  PubMed  CAS  Google Scholar 

  34. Brambila-Tapia AJ, Dávalos-Rodríguez IP, Gámez-Nava JI et al (2011) CD28 proximal promoter polymorphisms in systemic lupus erythematosus susceptibility. Rheumatol Int. doi:10.1007/s00296-011-1942-7

    Google Scholar 

  35. Lu Q, Wu A, Tesmer L et al (2007) Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol 179:6352–6358

    PubMed  CAS  Google Scholar 

  36. Zhou Y, Yuan J, Pan Y et al (2009) T cell CD40LG gene expression and the production of IgG by autologous B cells in systemic lupus erythematosus. Clin Immunol 132:362–370

    Article  PubMed  CAS  Google Scholar 

  37. Hikami K, Kawasaki A, Ito I et al (2011) Association of a functional polymorphism in the 3′-untranslated region of SPI1 with systemic lupus erythematosus. Arthritis Rheum 63:755–763

    Article  PubMed  CAS  Google Scholar 

  38. Wu B, Jin M, Zhang Y et al (2011) Evolution of the IL17 receptor family in chordates: a new subfamily IL17REL. Immunogenetics 63:835–845

    Article  PubMed  CAS  Google Scholar 

  39. Puwipirom H, Hirankarn N, Sodsai P et al (2010) Increased interleukin-23 receptor(+) T cells in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Arthritis Res Ther 12:R215

    Article  PubMed  CAS  Google Scholar 

  40. Parham C, Chirica M, Timans J et al (2002) A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168:5699–5708

    PubMed  CAS  Google Scholar 

  41. Safrany E, Hobor R, Jakab L et al (2010) Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients. Inflamm Res 59:159–164

    Article  PubMed  CAS  Google Scholar 

  42. Kim HS, Kim I, Kim JO et al (2009) No association between interleukin 23 receptor gene polymorphisms and systemic lupus erythematosus. Rheumatol Int 30:33–38

    Article  PubMed  CAS  Google Scholar 

  43. Sánchez E, Rueda B, Callejas JL et al (2007) Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus. Tissue Antigens 70:233–237

    Article  PubMed  Google Scholar 

  44. Unutmaz D (2009) RORC2: the master of human Th17 cell programming. Eur J Immunol 39:1452–1455

    Article  PubMed  CAS  Google Scholar 

  45. Lohr J, Knoechel B, Wang JJ et al (2006) Role of IL-17 and regulatory T lymphocytes in a systemic autoimmune disease. J Exp Med 203:2785–2791

    Article  PubMed  CAS  Google Scholar 

  46. Koenen HJ, Smeets RL, Vink PM et al (2008) Human CD25 high Foxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 112:2340–2352

    Article  PubMed  CAS  Google Scholar 

  47. Beriou G, Costantino CM, Ashley CW et al (2009) IL-17 producing human peripheral regulatory T cells retain suppressive function. Blood 113:4240–4249

    Article  PubMed  CAS  Google Scholar 

  48. Zhou X, Kong N, Wang J et al (2010) Cutting edge: all-trans retinoic acid sustains the stability and function of natural regulatory T cells in an inflammatory milieu. J Immunol 185:2675–2679

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81102192, 30830089), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20113420120008) and the Grants for Scientific Research of BSKY (No. XJ201014) from Anhui Medical University. We thank all the study subjects for their participation.

Conflict of interest

There is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dong-Qing Ye.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pan, HF., Leng, RX., Feng, CC. et al. Expression profiles of Th17 pathway related genes in human systemic lupus erythematosus. Mol Biol Rep 40, 391–399 (2013). https://doi.org/10.1007/s11033-012-2073-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2073-2

Keywords

Navigation