Skip to main content
Log in

The decreased frequency of SIGIRR-positive CD4+ T cells in peripheral blood of patients with SLE and its correlation with disease activity

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Recently, many studies have shown that Single immunoglobulin interleukin-1 receptor related protein (SIGIRR), a member of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling, affects autoimmune responses in animal model of systemic lupus erythematosus (SLE). However, the role of SIGIRR in the pathogenesis of human SLE has not been widely explored. In this study, we analyzed the frequency of SIGIRR-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) of SLE patients and its correlation with disease activity as well as the clinical data. Circulating SIGIRR-positive CD4+ T cells were quantified in 51 SLE patients and 38 healthy controls by using flow cytometer. Results showed that the percentages of SIGIRR-positive CD4+ T cells were decreased in the PBMCs of SLE patients compared with healthy controls (Z = −5.49, P < 0.001). The frequency of SIGIRR-positive CD4 + T cells were also significantly decreased in SLE patients with nephritis than those without nephritis (Z = −3.71, P < 0.001). In addition, there was significant correlation between the percentages of SIGIRR-positive CD4+ T cells and SLEDAI score (r s  = −0.74, P < 0.001), 24-hour urine protein (r s  = −0.62, P < 0.001), Scr (r s  = −0.65, P < 0.001), ESR (r s  = −0.60, P < 0.001), C3 (r s  = 0.53, P < 0.001) as well as C4 (r s  = 0.52, P < 0.001). However, there was no correlation between the proportion of SIGIRR-positive CD4+ T cells and glucocorticoid dose (P = 0.59). In summary, decreased numbers of SIGIRR-positive CD4+ T cells in SLE patients and its correlation with SLEDAI score as well as the clinical data suggest that SIGIRR 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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kotzin BL (1996) Systemic lupus erythematosus. Cell 85:303–306

    Article  CAS  PubMed  Google Scholar 

  2. D’Cruz DP, Khamashta MA, Hughes GR (2007) Systemic lupus erythematosus. Lancet 369:587–596

    Article  PubMed  Google Scholar 

  3. Goodnow CC (2007) Multistep pathogenesis of autoimmune disease. Cell 130:25–35

    Article  CAS  PubMed  Google Scholar 

  4. Thomassen E, Renshaw BR, Sims JE (1999) Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine 11:389–399

    Article  CAS  PubMed  Google Scholar 

  5. Polentarutti N, Rol GP, Muzio M et al (2003) Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR. Eur Cytokine Netw 14:211–218

    CAS  PubMed  Google Scholar 

  6. Huang X, Hazlett LD, Du W et al (2006) SIGIRR promotes resistance against Pseudomonas aeruginosa keratitis by down-regulating type-1 immunity and IL-1R1 and TLR4 signaling. J Immunol 177:548–556

    Article  CAS  PubMed  Google Scholar 

  7. Qin J, Qian Y, Yao J et al (2005) SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms. J Biol Chem 280:25233–25241

    Article  CAS  PubMed  Google Scholar 

  8. Zhang C, Wu X, Zhao Y et al (2011) SIGIRR inhibits toll-like receptor 4, 5, 9-mediated immune responses in human airway epithelial cells. Mol Biol Rep 38:601–609

    Article  CAS  PubMed  Google Scholar 

  9. Adib-Conquy M, Adrie C, Fitting C et al (2006) Up-regulation of MyD88s and SIGIRR, molecules inhibiting Toll-like receptor signaling, in monocytes from septic patients. Crit Care Med 34:2377–2385

    Article  CAS  PubMed  Google Scholar 

  10. Garlanda C, Riva F, Veliz T et al (2007) Increased susceptibility to colitis-associated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family. Cancer Res 67:6017–6021

    Article  CAS  PubMed  Google Scholar 

  11. Drexler SK, Kong P, Inglis J et al (2010) SIGIRR/TIR-8 is an inhibitor of toll-like receptor signaling in primary human cells and regulates inflammation in models of rheumatoid arthritis. Arthritis Rheum 62:2249–2261

    Article  CAS  PubMed  Google Scholar 

  12. Lech M, Kulkarni OP, Pfeiffer S et al (2008) Tir8/Sigirr prevents murine lupus by suppressing the immuno stimulatory effects of lupus autoantigens. J Exp Med 205:1879–1888

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Lech M, Skuginna V, Kulkarni OP et al (2010) Lack of SIGIRR/TIR8 aggravates hydrocarbon oil-induced lupus nephritis. J Pathol 220:596–607

    Article  CAS  PubMed  Google Scholar 

  14. Zhu YY, Su Y, Li ZG et al (2012) The largely normal response to Toll-like receptor 7 and 9 stimulation and the enhanced expression of SIGIRR by B cells in systemic lupus erythematosus. PLoS ONE 7:e44131

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Villena J, Suzuki R, Fujie H et al (2012) Immunobiotic Lactobacillus jensenii modulates the Toll-like receptor 4-induced inflammatory response via negative regulation in porcine antigen-presenting cells. Clin Vaccine Immunol 19:1038–1053

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Bombardier C, Gladman DD, Urowitz MB et al (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  CAS  PubMed  Google Scholar 

  18. 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  CAS  PubMed  Google Scholar 

  19. 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 

  20. Kadota C, Ishihara S, Aziz MM et al (2010) Down-regulation of single immunoglobulin interleukin-1R-related molecule (SIGIRR)/TIR8 expression in intestinal epithelial cells during inflammation. Clin Exp Immunol 162:348–361

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Zhao J, Zepp J, Bulek K et al (2011) SIGIRR, a negative regulator of colon tumorigenesis. Drug Discov Today Dis Mech 8:e63–e69

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Veliz Rodriguez T, Moalli F, Polentarutti N et al (2012) Role of Toll interleukin-1 receptor (IL-1R) 8, a negative regulator of IL-1R/Toll-like receptor signaling, in resistance to acute Pseudomonas aeruginosa lung infection. Infect Immun 80:100–109

    Article  PubMed Central  PubMed  Google Scholar 

  23. Noris M, Cassis P, Azzollini N et al (2009) The Toll-IL-1R member Tir8/SIGIRR negatively regulates adaptive immunity against kidney grafts. J Immunol 183:4249–4260

    Article  CAS  PubMed  Google Scholar 

  24. Garlanda C, Anders HJ, Mantovani A (2009) TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization. Trends Immunol 30:439–446

    Article  CAS  PubMed  Google Scholar 

  25. Bozza S, Zelante T, Moretti S et al (2008) Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection. J Immunol 180:4022–4031

    Article  CAS  PubMed  Google Scholar 

  26. Bulek K, Swaidani S, Qin J et al (2009) The essential role of single Ig IL-1 receptor-related molecule/Toll IL-1R8 in regulation of Th2 immune response. J Immunol 182:2601–2609

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Garlanda C, Riva F, Polentarutti N et al (2004) Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc Natl Acad Sci USA 101:3522–3526

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Xiao H, Yin W, Khan MA et al (2010) Loss of single immunoglobulin interlukin-1 receptor-related molecule leads to enhanced colonic polyposis in Apc(min) mice. Gastroenterology 139:574–585

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Lech M, Garlanda C, Mantovani A et al (2007) Different roles of TiR8/Sigirr on toll-like receptor signaling in intrarenal antigen-presenting cells and tubular epithelial cells. Kidney Int 72:182–192

    Article  CAS  PubMed  Google Scholar 

  30. Skuginna V, Lech M, Allam R et al (2011) Toll-like receptor signaling and SIGIRR in renal fibrosis upon unilateral ureteral obstruction. PLoS ONE 6:e19204

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Lech M, Avila-Ferrufino A, Allam R et al (2009) Resident dendritic cells prevent postischemic acute renal failure by help of single Ig IL-1 receptor-related protein. J Immunol 183:4109–4118

    Article  CAS  PubMed  Google Scholar 

  32. Tsao JT, Hsieh SC, Chiang BL et al (2012) Altered IL-10 and TNF-alpha production in peripheral blood mononuclear cells of systemic lupus erythematosus patients after Toll-like receptor 2, 4, or 9 activation. Clin Exp Med 12:153–158

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Postdoctoral Science Foundation of China (2012M511399) and the National Science Foundation (30830089, 81102192).

Conflict of interest

The authors declared no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to De-Guang Wang or Dong-Qing Ye.

Additional information

Dao-Yang Wang and Chao Su have contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, DY., Su, C., Chen, GM. et al. The decreased frequency of SIGIRR-positive CD4+ T cells in peripheral blood of patients with SLE and its correlation with disease activity. Mol Biol Rep 42, 423–430 (2015). https://doi.org/10.1007/s11033-014-3783-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3783-4

Keywords

Navigation