Archives of Dermatological Research

, Volume 301, Issue 1, pp 83–86 | Cite as

Type I interferon-associated cytotoxic inflammation in cutaneous lupus erythematosus

  • Joerg Wenzel
  • Sabine Zahn
  • Thomas Bieber
  • Thomas Tüting
Review

Abstract

Inappropriate activation of innate immune mechanisms, in particular of the type I interferon (IFN) system, is regarded to play an important role in the pathogenesis of lupus erythematosus (LE). Type I IFN serum levels have been shown to correlate with the disease activity in systemic LE and additionally play a proinflammatory role in the development of LE skin lesions. Recent studies demonstrated a close morphological association between the expression pattern of IFN-inducible chemokines (MxA, CXCL10) and typical histological features of cutaneous LE. These and other studies suggest that a complex network of IFN-associated cytokines, chemokines and adhesion molecules orchestrates and promotes tissue injury observed in LE skin.

Keywords

Skin Lupus CXCL9 CXCL10 CXCR3 

Notes

Conflict of interest statement

The authors have no potential conflict of interest.

References

  1. 1.
    Adam C, Thoua Y, Ronco P et al (1980) The effect of exogenous interferon: acceleration of autoimmune and renal diseases in (NZB/W) F1 mice. Clin Exp Immunol 40:373–382PubMedGoogle Scholar
  2. 2.
    Arrue I, Saiz A, Ortiz-Romero PL et al (2007) Lupus-like reaction to interferon at the injection site: report of five cases. J Cutan Pathol 34(Suppl 1):18–21. doi:10.1111/j.1600-0560.2007.00715.x PubMedCrossRefGoogle Scholar
  3. 3.
    Asselin-Paturel C, Brizard G, Chemin K et al (2005) Type I interferon dependence of plasmacytoid dendritic cell activation and migration. J Exp Med 201:1157–1167. doi:10.1084/jem.20041930 PubMedCrossRefGoogle Scholar
  4. 4.
    Baechler EC, Batliwalla FM, Karypis G et al (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA 100:2610–2615. doi:10.1073/pnas.0337679100 PubMedCrossRefGoogle Scholar
  5. 5.
    Bennett L, Palucka AK, Arce E et al (2003) Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 197:711–723. doi:10.1084/jem.20021553 PubMedCrossRefGoogle Scholar
  6. 6.
    Blomberg S, Eloranta ML, Cederblad B et al (2001) Presence of cutaneous interferon-alpha producing cells in patients with systemic lupus erythematosus. Lupus 10:484–490. doi:10.1191/096120301678416042 PubMedCrossRefGoogle Scholar
  7. 7.
    Braun D, Geraldes P, Demengeot J (2003) Type I Interferon controls the onset and severity of autoimmune manifestations in lpr mice. J Autoimmun 20:15–25. doi:10.1016/S0896-8411(02)00109-9 PubMedCrossRefGoogle Scholar
  8. 8.
    Clark-Lewis I, Mattioli I, Gong JH et al (2003) Structure–function relationship between the human chemokine receptor CXCR3 and its ligands. J Biol Chem 278:289–295. doi:10.1074/jbc.M209470200 PubMedCrossRefGoogle Scholar
  9. 9.
    Costedoat-Chalumeau N, Amoura Z, Hulot JS et al (2006) Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum 54:3284–3290. doi:10.1002/art.22156 PubMedCrossRefGoogle Scholar
  10. 10.
    Dall’era MC, Cardarelli PM, Preston BT et al (2005) Type I interferon correlates with serological and clinical manifestations of SLE. Ann Rheum Dis 64:1692–1697. doi:10.1136/ard.2004.033753 PubMedCrossRefGoogle Scholar
  11. 11.
    Fah J, Pavlovic J, Burg G (1995) Expression of MxA protein in inflammatory dermatoses. J Histochem Cytochem 43:47–52PubMedGoogle Scholar
  12. 12.
    Farkas L, Beiske K, Lund-Johansen F et al (2001) Plasmacytoid dendritic cells (natural interferon-alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol 159:237–243PubMedGoogle Scholar
  13. 13.
    Graham RR, Kozyrev SV, Baechler EC et al (2006) A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 38:550–555. doi:10.1038/ng1782 PubMedCrossRefGoogle Scholar
  14. 14.
    Guillot B, Portales P, Du Thanh A et al (2005) The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-alpha treatment. Br J Dermatol 152:690–696. doi:10.1111/j.1365-2133.2005.06512.x PubMedCrossRefGoogle Scholar
  15. 15.
    Hasegawa K, Hayashi T (2003) Synthetic CpG oligodeoxynucleotides accelerate the development of lupus nephritis during preactive phase in NZB x NZWF1 mice. Lupus 12:838–845. doi:10.1191/0961203303lu483oa PubMedCrossRefGoogle Scholar
  16. 16.
    Hooks JJ, Moutsopoulos HM, Geis SA et al (1979) Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med 301:5–8PubMedGoogle Scholar
  17. 17.
    Iijima W, Ohtani H, Nakayama T et al (2003) Infiltrating CD8+ T cells in oral lichen planus predominantly express CCR5 and CXCR3 and carry respective chemokine ligands RANTES/CCL5 and IP-10/CXCL10 in their cytolytic granules: a potential self-recruiting mechanism. Am J Pathol 163:261–268PubMedGoogle Scholar
  18. 18.
    Kuhn A, Herrmann M, Kleber S et al (2006) Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation. Arthritis Rheum 54:939–950. doi:10.1002/art.21658 PubMedCrossRefGoogle Scholar
  19. 19.
    Kuhn A, Sonntag M, Lehmann P et al (2002) Characterization of the inflammatory infiltrate and expression of endothelial cell adhesion molecules in lupus erythematosus tumidus. Arch Dermatol Res 294:6–13. doi:10.1007/s00403-001-0286-7 PubMedCrossRefGoogle Scholar
  20. 20.
    Kuhn A, Sonntag M, Sunderkotter C et al (2002) Upregulation of epidermal surface molecule expression in primary and ultraviolet-induced lesions of lupus erythematosus tumidus. Br J Dermatol 146:801–809. doi:10.1046/j.1365-2133.2002.04693.x PubMedCrossRefGoogle Scholar
  21. 21.
    Lovgren T, Eloranta ML, Bave U et al (2004) Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum 50:1861–1872. doi:10.1002/art.20254 PubMedCrossRefGoogle Scholar
  22. 22.
    Lovgren T, Eloranta ML, Kastner B et al (2006) Induction of interferon-alpha by immune complexes or liposomes containing systemic lupus erythematosus autoantigen- and Sjogren’s syndrome autoantigen-associated RNA. Arthritis Rheum 54:1917–1927. doi:10.1002/art.21893 PubMedCrossRefGoogle Scholar
  23. 23.
    Meller S, Winterberg F, Gilliet M et al (2005) Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: an amplification cycle triggering cutaneous lupus erythematosus. Arthritis Rheum 52:1504–1516. doi:10.1002/art.21034 PubMedCrossRefGoogle Scholar
  24. 24.
    Munoz LE, Gaipl US, Franz S et al (2005) SLE—a disease of clearance deficiency? Rheumatology (Oxford) 44:1101–1107. doi:10.1093/rheumatology/keh693 CrossRefGoogle Scholar
  25. 25.
    Nyberg F, Hasan T, Skoglund C et al (1999) Early events in ultraviolet light-induced skin lesions in lupus erythematosus: expression patterns of adhesion molecules ICAM-1, VCAM-1 and E-selectin. Acta Derm Venereol 79:431–436. doi:10.1080/000155599750009852 PubMedCrossRefGoogle Scholar
  26. 26.
    Nyberg F, Stephansson E (1999) Elevated soluble E-selectin in cutaneous lupus erythematosus. Adv Exp Med Biol 455:153–159PubMedGoogle Scholar
  27. 27.
    Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939. doi:10.1056/NEJMra071297 PubMedCrossRefGoogle Scholar
  28. 28.
    Ronnblom L, Eloranta ML, Alm GV (2006) The type I interferon system in systemic lupus erythematosus. Arthritis Rheum 54:408–420. doi:10.1002/art.21571 PubMedCrossRefGoogle Scholar
  29. 29.
    Santiago-Raber ML, Baccala R, Haraldsson KM et al (2003) Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. J Exp Med 197:777–788. doi:10.1084/jem.20021996 PubMedCrossRefGoogle Scholar
  30. 30.
    Smit MJ, Verdijk P, van der Raaij-Helmer EM et al (2003) CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood 102:1959–1965. doi:10.1182/blood-2002-12-3945 PubMedCrossRefGoogle Scholar
  31. 31.
    Sontheimer RD, Thomas JR, Gilliam JN (1979) Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol 115:1409–1415. doi:10.1001/archderm.115.12.1409 PubMedCrossRefGoogle Scholar
  32. 32.
    Tebbe B, Mazur L, Stadler R et al (1995) Immunohistochemical analysis of chronic discoid and subacute cutaneous lupus erythematosus—relation to immunopathological mechanisms. Br J Dermatol 132:25–31. doi:10.1111/j.1365-2133.1995.tb08620.x PubMedCrossRefGoogle Scholar
  33. 33.
    Wenzel J, Henze S, Brahler S et al (2005) The expression of human leukocyte antigen-DR and CD25 on circulating T cells in cutaneous lupus erythematosus and correlation with disease activity. Exp Dermatol 14:454–459. doi:10.1111/j.0906-6705.2005.00301.x PubMedCrossRefGoogle Scholar
  34. 34.
    Wenzel J, Henze S, Wörrenkämper E et al (2005) Role of the chemokine receptor CCR4 and its ligand TARC/CCL17 for lymphocyte recruitment in cutaneous lupus erythematosus. J Invest Dermatol 124:1241–1248. doi:10.1111/j.0022-202X.2005.23755.x PubMedCrossRefGoogle Scholar
  35. 35.
    Wenzel J, Tuting T (2008) An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in “interface dermatitis”. J Invest Dermatol (in press), 17 April 2008 [Epub ahead of print]Google Scholar
  36. 36.
    Wenzel J, Tuting T (2007) Identification of type I interferon-associated inflammation in the pathogenesis of cutaneous lupus erythematosus opens up options for novel therapeutic approaches. Exp Dermatol 16:454–463. doi:10.1111/j.1600-0625.2007.00556.x PubMedCrossRefGoogle Scholar
  37. 37.
    Wenzel J, Uerlich M, Worrenkamper E et al (2005) Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA. Br J Dermatol 153:1011–1015. doi:10.1111/j.1365-2133.2005.06784.x PubMedCrossRefGoogle Scholar
  38. 38.
    Wenzel J, Worenkamper E, Freutel S et al (2005) Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus. J Pathol 205:435–442. doi:10.1002/path.1721 PubMedCrossRefGoogle Scholar
  39. 39.
    Wenzel J, Zahn S, Mikus S et al (2007) The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsets. Br J Dermatol 157:752–757. doi:10.1111/j.1365-2133.2007.08137.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Joerg Wenzel
    • 1
  • Sabine Zahn
    • 1
  • Thomas Bieber
    • 1
  • Thomas Tüting
    • 1
  1. 1.Department of DermatologyUniversity of BonnBonnGermany

Personalised recommendations