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Type 17 T-helper cells might be a promising therapeutic target for systemic lupus erythematosus

Nature Clinical Practice Rheumatology volume 4, pages 352–353 (2008)Cite this article

Systemic lupus erythematosus (SLE) is a prototypic, systemic, autoimmune disease, characterized by a diverse array of autoantibody production, complement activation and immune-complex deposition, which causes tissue and organ damage. The etiology and pathogenetic mechanisms of SLE have not been clearly elucidated. At present, there is no cure for SLE and treatment is aimed at controlling symptoms; despite this, exploration into the disease mechanisms might lead to the development of improved therapies.1

Cytokines produced by abnormal T-helper (TH) cells have been shown to be involved in the pathogenesis of SLE and other autoimmune diseases. Activated autoreactive TH cells assist autoreactive B cells to differentiate and produce pathogenic autoantibodies.2 Autoantibody-containing immune complexes and the direct effects of inflammatory TH cells promote tissue injury and organ damage. Models of human autoimmune disease, including experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA), have been recognized as prototypic CD4+ TH1-cell-mediated diseases. Nevertheless, there are contradictions in the published literature regarding the link between TH1-cell function and autoimmune inflammation.3,4 In one study, mice that lacked components of the interleukin (IL)-12–interferon (IFN)-γ axis developed EAE and CIA of normal or even increased magnitude. By contrast, mice that lacked the p40 subunit shared by IL-12 and IL-23 were resistant to EAE and CIA, and antibodies against this p40 subunit significantly suppressed the development of autoimmune disease.3

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References

  1. Cook HT and Botto M (2006) Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus. Nat Clin Pract Rheumatol 2: 330–337

    Article  CAS  Google Scholar 

  2. Datta SK et al. (2005) T-helper cell intrinsic defects in lupus that break peripheral tolerance to nuclear autoantigens. J Mol Med 83: 267–278

    Article  CAS  Google Scholar 

  3. Kikly K et al. (2006) The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 18: 670–675

    Article  CAS  Google Scholar 

  4. Hunter CA (2005) New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol 5: 521–531

    Article  CAS  Google Scholar 

  5. Kramer JM and Gaffen SL (2007) Interleukin-17: a new paradigm in inflammation, autoimmunity, and therapy. J Periodontol 78: 1083–1093

    Article  Google Scholar 

  6. Nakae S et al. (2003) Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 171: 6173–6177

    Article  CAS  Google Scholar 

  7. Lubberts E et al. (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50: 650–659

    Article  CAS  Google Scholar 

  8. McGeachy MJ et al. (2007) TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8: 1390–1397

    Article  CAS  Google Scholar 

  9. Huber AK et al. (2008) Interleukin (IL)-23 receptor is a major susceptibility gene for graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab 93: 1077–1088

    Article  CAS  Google Scholar 

  10. Wong CK 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  CAS  Google Scholar 

  11. Dong G et al. (2003) IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Chin Med J (Engl) 116: 543–548

    CAS  Google Scholar 

  12. Hsu HC et al. (2008) Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 9: 166–175

    Article  CAS  Google Scholar 

  13. Mangini AJ et al. (2007) Type I interferons inhibition of inflammatory T helper cell responses in systemic lupus erythematosus. Ann N Y Acad Sci 1108: 11–23

    Article  CAS  Google Scholar 

  14. Korn T et al. (2007) Th17 cells: effector T cells with inflammatory properties. Semin Immunol 19: 362–371

    Article  CAS  Google Scholar 

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Acknowledgements

This work was partly supported by grants from the National Natural Science Foundation of China (30571608, 30771848) and the Natural Science Foundation of Anhui Province (070413109).

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Authors and Affiliations

  1. HF Pan is a Doctor and DQ Ye is a Professor in the Department of Epidemiology and Biostatistics, and XP Li is a Rheumatologist in the Department of Rheumatology, Anhui Provincial Hospital, Hefei, Anhui, China.,

    Hai Feng Pan, Dong Qing Ye & Xiang Pei Li

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  1. Hai Feng Pan
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Correspondence to Dong Qing Ye.

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Pan, H., Ye, D. & Li, X. Type 17 T-helper cells might be a promising therapeutic target for systemic lupus erythematosus. Nat Rev Rheumatol 4, 352–353 (2008). https://doi.org/10.1038/ncprheum0815

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