Network of Myeloid and Plasmacytoid Dendritic Cells in Atopic Dermatitis

  • Natalija Novak
  • Wenming Peng
  • Chunfeng Yu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)


Atopic dermatitis (AD) presents as a chronic relapsing skin disease with high prevalence in children. The typical distributed skin lesions make the clinical diagnosis of AD very simple and clear-cut in most of the cases. In contrast, the underlying mechanisms leading to the manifestation of AD are more than complex and consist of genetic components combined with various deficiencies on the level of innate and adaptive immune mechanisms. Challenged by this puzzle, scientific approaches of the last years have made considerable progress in gaining insights into the mechanisms, which cause AD. AD is a biphasic inflammatory skin disease characterized by an initial phase predominated by Th2 cytokines which switches into a second, more chronic Th1-dominated eczematous phase. Two different dendritic cell (DC) subtypes bearing the high-affinity receptor for IgE (Fcε RI) have been identified in the epidermal skin of AD patients: Fcε RIhigh Langerhans cells (LCs) and Fcε RIhigh inflammatory dendritic epidermal cells (IDECs). These two DC subtypes are believed to contribute distinctly to the biphasic nature and the outcome of T cell responses in AD. In contrast, plasmacytoid DCs, which play an important role in the defence against viral infections, have been shown to bear the high-affinity receptor for IgE too but are nearly absent from the epidermal skin lesions of AD patients. In light of recent developments, the picture emerges that different IgE-receptor bearing DC subtypes in the blood and skin of AD patients play a pivotal role in the complex network of DCs, which is highlighted in this review.


Dendritic Cell Atopic Dermatitis Allergen Challenge Plasmacytoid Dendritic Cell Atopy Patch Test 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Bieber, T., de la Salle, H., Wollenberg, A., Hakimi, J., Chizzonite, R., Ring, J., Hanau, D. and de la Salle, C. (1992) Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J. Exp. Med. 175, 1285–1290.CrossRefPubMedGoogle Scholar
  2. Bonasio, R. and von Andrian, U.H. (2006) Generation, migration and function of circulating dendritic cells. Curr. Opin. Immunol. 18, 503–511.CrossRefPubMedGoogle Scholar
  3. Cookson, W. (2004) The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat. Rev. Immunol. 4, 978–988.CrossRefPubMedGoogle Scholar
  4. Cork, M.J., Robinson, D.A., Vasilopoulos, Y., Ferguson, A., Moustafa, M., MacGowan, A., Duff, G.W., Ward, S.J. and Tazi-Ahnini, R. (2006) New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. J. Allergy Clin. Immunol. 118, 3–21.CrossRefPubMedGoogle Scholar
  5. Grewe, M., Walther, S., Gyufko, K., Czech, W., Schopf, E. and Krutmann, J. (1995) Analysis of the cytokine pattern expressed in situ in inhalant allergen patch test reactions of atopic dermatitis patients. J. Invest. Dermatol. 105, 407–410.CrossRefPubMedGoogle Scholar
  6. Gunther, C., Bello-Fernandez, C., Kopp, T., Kund, J., Carballido-Perrig, N., Hinteregger, S., Fassl, S., Schwarzler, C., Lametschwandtner, G., Stingl, G., Biedermann, T. and Carballido, J.M. (2005) CCL18 is expressed in atopic dermatitis and mediates skin homing of human memory T cells. J. Immunol. 174, 1723–1728.PubMedGoogle Scholar
  7. Homey, B., Steinhoff, M., Ruzicka, T. and Leung, D.Y. (2006) Cytokines and chemokines orchestrate atopic skin inflammation. J. Allergy Clin. Immunol. 118, 178–189.CrossRefPubMedGoogle Scholar
  8. Howell, M.D., Wollenberg, A., Gallo, R.L., Flaig, M., Streib, J.E., Wong, C., Pavicic, T., Boguniewicz, M. and Leung, D.Y. (2006) Cathelicidin deficiency predisposes to eczema herpeticum. J. Allergy Clin. Immunol. 117, 836–841.CrossRefPubMedGoogle Scholar
  9. Jolles, S. (2002) Paul Langerhans. J. Clin. Pathol. 55, 243.PubMedGoogle Scholar
  10. Kerschenlohr, K., Decard, S., Przybilla, B. and Wollenberg, A. (2003) Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis. J. Allergy Clin. Immunol. 111, 869–874.CrossRefPubMedGoogle Scholar
  11. Leung, D.Y. and Bieber, T. (2003) Atopic dermatitis. Lancet 361, 151–160.CrossRefPubMedGoogle Scholar
  12. Mothes, N., Niggemann, B., Jenneck, C., Hagemann, T., Weidinger, S., Bieber, T., Valenta, R. and Novak, N. (2005) The cradle of IgE autoreactivity in atopic eczema lies in early infancy. J. Allergy Clin. Immunol. 116, 706–709.CrossRefPubMedGoogle Scholar
  13. Novak, N., Allam, J.P., Hagemann, T., Jenneck, C., Laffer, S., Valenta, R., Kochan, J. and Bieber, T. (2004a) Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis. J. Allergy Clin. Immunol. 114, 364–370.CrossRefPubMedGoogle Scholar
  14. Novak, N., Valenta, R., Bohle, B., Laffer, S., Haberstok, J., Kraft, S. and Bieber, T. (2004b) FcepsilonRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T cell phenotypes in vitro. J. Allergy Clin. Immunol. 113, 949–957.CrossRefPubMedGoogle Scholar
  15. Novak, N., Bieber, T. and Leung, D.Y. (2003a) Immune mechanisms leading to atopic dermatitis. J. Allergy Clin. Immunol. 112, S128–S139.CrossRefPubMedGoogle Scholar
  16. Novak, N., Kraft, S. and Bieber, T. (2003b) Unraveling the mission of FcepsilonRI on antigen-presenting cells. J. Allergy. Clin. Immunol. 111, 38–44.CrossRefPubMedGoogle Scholar
  17. Novak, N., Tepel, C., Koch, S., Brix, K., Bieber, T.,and Kraft, S. (2003c) Evidence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic donors. J. Clin. Invest. 111, 1047–1056.PubMedGoogle Scholar
  18. Novak, N., Kwiek, B. and Bieber, T. (2005) The mode of topical immunomodulators in the immunological network of atopic dermatitis. Clin. Exp. Dermatol. 30, 160–164.CrossRefPubMedGoogle Scholar
  19. Novak, N. and Peng, W. (2005) Dancing with the enemy: the interplay of herpes simplex virus with dendritic cells. Clin. Exp. Immunol. 142, 405–410.PubMedGoogle Scholar
  20. Ong, P.Y., Ohtake, T., Brandt, C., Strickland, I., Boguniewicz, M., Ganz, T., Gallo, R.L. and Leung, D.Y. (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N. Engl. J. Med. 347, 1151–1160.CrossRefPubMedGoogle Scholar
  21. Palmer, C.N., Irvine, A.D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S.P., Goudie, D.R., Sandilands, A., Campbell, L.E., Smith, F.J., O’Regan, G.M., Watson, R.M., Cecil, J.E., Bale, S.J., Compton, J.G., DiGiovanna, J.J., Fleckman, P., Lewis-Jones, S., Arseculeratne, G., Sergeant, A., Munro, C.S., El, H.B., McElreavey, K., Halkjaer, L.B., Bisgaard, H., Mukhopadhyay, S. and McLean, W.H. (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat. Genet. 38, 441–446.CrossRefPubMedGoogle Scholar
  22. Pivarcsi, A., Gombert, M., Dieu-Nosjean, M.C., Lauerma, A., Kubitza, R., Meller, S., Rieker, J., Muller, A., Da, C.L., Haahtela, A., Sonkoly, E., Fridman, W.H., Alenius, H., Kemeny, L., Ruzicka, T., Zlotnik, A. and Homey, B. (2004) CC chemokine ligand 18, an atopic dermatitis-associated and dendritic cell-derived chemokine, is regulated by staphylococcal products and allergen exposure. J. Immunol. 173, 5810–5817.PubMedGoogle Scholar
  23. Schroeder, J.T., Bieneman, A.P., Xiao, H., Chichester, K.L., Vasagar, K., Saini, S. and Liu, M.C. (2005) TLR9- and FcepsilonRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression. J. Immunol. 175, 5724–5731.PubMedGoogle Scholar
  24. Schuller, E., Oppel, T., Bornhovd, E., Wetzel, C. and Wollenberg, A. (2004) Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no Langerhans cell apoptosis in patients with atopic dermatitis. J. Allergy Clin. Immunol. 114, 137–143.CrossRefPubMedGoogle Scholar
  25. Simon, D., Vassina, E., Yousefi, S., Kozlowski, E., Braathen, L.R. and Simon, H.U. (2004) Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment. J. Allergy Clin. Immunol. 114, 887–895.CrossRefPubMedGoogle Scholar
  26. Soumelis, V. and Liu, Y.J. (2006) From plasmacytoid to dendritic cell: morphological and functional switches during plasmacytoid pre-dendritic cell differentiation. Eur. J. Immunol. 36, 2286–2292.CrossRefPubMedGoogle Scholar
  27. Stary, G., Bangert, C., Stingl, G. and Kopp, T. (2005) Dendritic cells in atopic dermatitis: expression of FcepsilonRI on two distinct inflammation-associated subsets. Int. Arch. Allergy Immunol. 138, 278–290.CrossRefPubMedGoogle Scholar
  28. Strid, J. and Strobel, S. (2005) Skin barrier dysfunction and systemic sensitization to allergens through the skin. Cur. Drug Targets Inflamm. Allergy 4, 531–541.CrossRefGoogle Scholar
  29. Villadangos, J.A. and Heath, W.R. (2005) Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: limitations of the Langerhans cells paradig. Semin. Immunol. 17, 262–272.CrossRefPubMedGoogle Scholar
  30. Wang, B., Rieger, A., Kilgus, O., Ochiai, K., Maurer, D., Fodinger, D., Kinet, J.P. and Stingl, G. (1992) Epidermal Langerhans cells from normal human skin bind monomeric IgE via Fc epsilon receptor. J. Exp. Med. 175, 1353–1365.CrossRefPubMedGoogle Scholar
  31. Wang, Y.H., Ito, T., Wang, Y.H., Homey, B., Watanabe, N., Martin, R., Barnes, C.J., McIntyre, B.W., Gilliet, M., Kumar, R., Yao, Z. and Liu, Y.J. (2006) Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity 24, 827–838.CrossRefPubMedGoogle Scholar
  32. Weidinger, S., Illig, T., Baurecht, H., Irvine, A.D., Rodriguez, E., Diaz-Lacava, A., Klopp, N., Wagenpfeil, S., Zhao, Y., Liao, H., Lee, S.P., Palmer, C.N., Jenneck, C., Maintz, L., Hagemann, T., Behrendt, H., Ring, J., Nothen, M.M., McLean, W.H. and Novak, N. (2006) Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J. Allergy Clin. Immunol. 118, 214–219.CrossRefPubMedGoogle Scholar
  33. Wollenberg, A., Wagner, M., Gunther, S., Towarowski, A., Tuma, E., Moderer, M., Rothenfusser, S., Wetzel, S., Endres, S. and Hartmann, G. (2002) Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J. Invest. Dermatol. 119, 1096–1102.CrossRefPubMedGoogle Scholar
  34. Wollenberg, A., Wen, S. and Bieber, T. (1995) Langerhans cell phenotyping: a new tool for differential diagnosis of inflammatory skin diseases [letter]. Lancet 346, 1626–1627.CrossRefPubMedGoogle Scholar
  35. Wollenberg, A., Zoch, C., Wetzel, S., Plewig, G. and Przybilla, B. (2003) Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases. J. Am. Acad. Dermatol. 49, 198–205.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of DermatologyUniversity of BonnBonnGermany

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