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T-Helper Cells pp 171-185 | Cite as

Aldara-Induced Psoriasis-Like Skin Inflammation: Isolation and Characterization of Cutaneous Dendritic Cells and Innate Lymphocytes

  • C. T. Wohn
  • S. Pantelyushin
  • J. L. Ober-Blöbaum
  • B. E. Clausen
Part of the Methods in Molecular Biology book series (MIMB, volume 1193)

Abstract

Psoriasis is a chronic auto-inflammatory skin disease of unknown etiology affecting millions of people worldwide. Dissecting the cellular networks and molecular signals promoting the development of psoriasis critically depends on appropriate animal models. Topical application of Aldara cream containing the Toll-like receptor (TLR)7-ligand Imiquimod induces skin inflammation and pathology in mice closely resembling plaque-type psoriasis in humans. The particular power of the Aldara model lies in examining the early events during psoriatic plaque formation, which is difficult to achieve in patients. Hence, recent reports using this model have challenged currently prevailing concepts concerning the pathophysiology of psoriasis. Here, we describe the induction and phenotype of Aldara-mediated dermatitis in mice and, in particular, analysis of the inflammatory cell infiltrate using flow cytometry.

Key words

Aldara cream Dendritic cells γδ T cells Imiquimod Innate lymphocytes Psoriasis Psoriatic skin inflammation 

References

  1. 1.
    Perera GK, Di Meglio P, Nestle FO (2012) Psoriasis. Annu Rev Pathol Mech Dis 7:385–422CrossRefGoogle Scholar
  2. 2.
    Schön MP (2008) Animal models of psoriasis: a critical appraisal. Exp Dermatol 17:703–712PubMedCrossRefGoogle Scholar
  3. 3.
    Gilliet M, Conrad C, Geiges M et al (2004) Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 140:1490–1495PubMedGoogle Scholar
  4. 4.
    van der Fits L, Mourits S, Voerman JSA et al (2009) Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 Axis. J Immunol 182:5836–5845PubMedCrossRefGoogle Scholar
  5. 5.
    Cai Y, Shen X, Ding C et al (2011) Pivotal role of dermal IL-17-producing γt T cells in skin inflammation. Immunity 35:596–610PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Pantelyushin S, Haak S, Ingold B et al (2012) Rorγt+innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice. J Clin Invest 122:2252–2256PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Wohn C, Ober-Blöbaum JL, Haak S et al (2013) Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. Proc Natl Acad Sci U S A 110(26):10723–10728PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Garman RD, Doherty PJ, Raulet DH (1986) Diversity, rearrangement, and expression of murine T cell gamma genes. Cell 45:733–742PubMedCrossRefGoogle Scholar
  9. 9.
    Heilig JS, Tonegawa S (1986) Diversity of murine gamma genes and expression in fetal and adult T lymphocytes. Nature 322:836–840PubMedCrossRefGoogle Scholar
  10. 10.
    Havran WL, Grell S, Duwe G et al (1989) Limited diversity of T-cell receptor gamma-chain expression of murine Thy-1+ dendritic epidermal cells revealed by V gamma 3-specific monoclonal antibody. Proc Natl Acad Sci U S A 86:4185–4189PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Gray EE, Suzuki K, Cyster JG (2011) Cutting edge: identification of a motile IL-17-producing T cell population in the dermis. J Immunol 186:6091–6095PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Sumaria N, Roediger B, Ng LG et al (2011) Cutaneous immunosurveillance by self-renewing dermal T cells. J Exp Med 208:505–518PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Vantourout P, Hayday A (2013) Six-of-the-best: unique contributions of γδ T cells to immunology. Nat Rev Immunol 13:88–100PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Bernink J, Mjösberg J, Spits H (2013) Th1- and Th2-like subsets of innate lymphoid cells. Immunol Rev 252:133–138PubMedCrossRefGoogle Scholar
  15. 15.
    Buonocore S, Ahern PP, Uhlig HH et al (2010) Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464:1371–1375PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Henri S, Poulin LF, Tamoutounour S et al (2010) CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells. J Exp Med 207:189–206PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Clausen BE, Kel JM (2010) Langerhans cells: critical regulators of skin immunity? Immunol Cell Biol 88:351–360PubMedCrossRefGoogle Scholar
  18. 18.
    Romani N, Clausen BE, Stoitzner P (2010) Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol Rev 234:120–141PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Langlet C, Tamoutounour S, Henri S et al (2012) CD64 expression distinguishes monocyte-derived and conventional dendritic cells and reveals their distinct role during intramuscular Immunization. J Immunol 188:1751–1760PubMedCrossRefGoogle Scholar
  20. 20.
    Plantinga M, Guilliams M, Vanheerswynghels M et al (2013) Conventional and monocyte-derived CD11b+ dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38:322–335PubMedCrossRefGoogle Scholar
  21. 21.
    Wollenberg A, Mommaas M, Oppel T et al (2002) Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases. J Invest Dermatol 118:327–334PubMedCrossRefGoogle Scholar
  22. 22.
    Cheong C, Matos I, Choi J-H et al (2010) Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209+ dendritic cells for immune T cell areas. Cell 143:416–429PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Burgdorf S, Schuette V, Semmling V et al (2010) Steady state cross-presentation of OVA is mannose receptor-dependent but inhibitable by collagen fragments. Proc Natl Acad Sci U S A 107:E48–E49PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Suzuki H, Wang B, Shivji GM et al (2000) Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J Invest Dermatol 114:135–141PubMedCrossRefGoogle Scholar
  25. 25.
    Domínguez P, Ardavín C (2010) Differentiation and function of mouse monocyte-derived dendritic cells in steady state and inflammation. Immunol Rev 234(90–104):1–15Google Scholar
  26. 26.
    Liu F, Whitton JL (2005) Cutting edge: re-evaluating the in vivo cytokine responses of CD8+ T cells during primary and secondary viral infections. J Immunol 174:5936–5940PubMedCrossRefGoogle Scholar
  27. 27.
    Heib V, Becker M, Warger T et al (2007) Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice. Blood 110:946–953PubMedCrossRefGoogle Scholar
  28. 28.
    Walter A, Schäfer M, Cecconi V et al (2013) Aldara activates TLR7-independent immune defence. Nat Commun 4:1560PubMedCrossRefGoogle Scholar
  29. 29.
    Berghöfer B, Frommer T, Haley G et al (2006) TLR7 ligands induce higher IFN-alpha production in females. J Immunol 177:2088–2096PubMedCrossRefGoogle Scholar
  30. 30.
    Karnam G, Rygiel TP, Raaben M et al (2012) CD200 receptor controls sex-specific TLR7 responses to viral infection. PLoS Pathog 8:e1002710PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Vonarbourg C, Mortha A, Bui VL et al (2010) Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt+ innate lymphocytes. Immunity 33:736–751PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • C. T. Wohn
    • 1
  • S. Pantelyushin
    • 2
  • J. L. Ober-Blöbaum
    • 3
  • B. E. Clausen
    • 3
  1. 1.Department of Immunology, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands
  2. 2.Institute of Experimental ImmunologyUniversity of ZürichZürichSwitzerland
  3. 3.Institute for Molecular MedicineUniversity Medical Center of the Johannes Gutenberg-University MainzMainzGermany

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