CCL1-CCR8 interactions: An axis mediating the recruitment of T cells and langerhans-type dendritic cells to sites of atopic skin inflammation

Michael Gombert, Marie Caroline Dieu-Nosjean, Franziska Winterberg, Erich Bünemann, Robert C. Kubitza, Ludivine Da Cunha, Anna Haahtela, Sari Lehtimäki, Anja Müller, Juliane Rieker, Stephan Meller, Andor Pivarcsi, Andrea Koreck, Wolf Herman Fridman, Hans Walter Zentgraf, Hermann Pavenstädt, Ali Amara, Christophe Caux, Lajos Kemeny, Harri AleniusAntti Lauerma, Thomas Ruzicka, Albert Zlotnik, Bernhard Homey

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152 Citations (Scopus)

Abstract

Atopic dermatitis represents a chronically relapsing skin disease with a steadily increasing prevalence of 10-20% in children. Skin-infiltrating T cells, dendritic cells (DC), and mast cells are thought to play a crucial role in its pathogenesis. We report that the expression of the CC chemokine CCL1 (I-309) is significantly and selectively up-regulated in atopic dermatitis in comparison to psoriasis, cutaneous lupus erythematosus, or normal skin. CCL1 serum levels of atopic dermatitis patients are significantly higher than levels in healthy individuals. DC, mast cells, and dermal endothelial cells are abundant sources of CCL1 during atopic skin inflammation and allergen challenge, and Staphylococcus aureus-derived products induce its production. In vitro, binding and cross-linking of IgE on mast cells resulted in a significant up-regulation of this inflammatory chemokine. Its specific receptor, CCR8, is expressed on a small subset of circulating T cells and is abundantly expressed on interstitial DC, Langerhans cells generated in vitro, and their monocytic precursors. Although DC maintain their CCR8+ status during maturation, brief activation of circulating T cells recruits CCR8 from intracytoplamic stores to the cell surface. Moreover, the inflammatory and atopy-associated chemokine CCL1 synergizes with the homeostatic chemokine CXCL12 (SDF-1α) resulting in the recruitment of T cell and Langerhans cell-like DC. Taken together, these findings suggest that the axis CCL1-CCR8 links adaptive and innate immune functions that play a role in the initiation and amplification of atopic skin inflammation.

Original languageEnglish
Pages (from-to)5082-5091
Number of pages10
JournalJournal of Immunology
Volume174
Issue number8
DOIs
Publication statusPublished - Apr 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gombert, M., Dieu-Nosjean, M. C., Winterberg, F., Bünemann, E., Kubitza, R. C., Da Cunha, L., Haahtela, A., Lehtimäki, S., Müller, A., Rieker, J., Meller, S., Pivarcsi, A., Koreck, A., Fridman, W. H., Zentgraf, H. W., Pavenstädt, H., Amara, A., Caux, C., Kemeny, L., ... Homey, B. (2005). CCL1-CCR8 interactions: An axis mediating the recruitment of T cells and langerhans-type dendritic cells to sites of atopic skin inflammation. Journal of Immunology, 174(8), 5082-5091. https://doi.org/10.4049/jimmunol.174.8.5082