Cellular immune response

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CXCL12 is essential for migration of activated Langerhans cells from epidermis to dermis

  1. Krista Ouwehand1,
  2. Saskia J. A. M. Santegoets2,
  3. Derk P. Bruynzeel1,
  4. Rik J. Scheper2,
  5. Tanja D. de Gruijl3,
  6. Susan Gibbs1,*

Article first published online: 16 OCT 2008

DOI: 10.1002/eji.200838384

Issue

European Journal of Immunology

European Journal of Immunology

Volume 38, Issue 11, pages 3050–3059, November 2008

Additional Information

How to Cite

Ouwehand, K., Santegoets, S. J. A. M., Bruynzeel, D. P., Scheper, R. J., de Gruijl, T. D. and Gibbs, S. (2008), CXCL12 is essential for migration of activated Langerhans cells from epidermis to dermis. Eur. J. Immunol., 38: 3050–3059. doi: 10.1002/eji.200838384

Author Information

  1. 1

    Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands

  2. 2

    Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands

  3. 3

    Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands

*Department of Dermatology, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands Fax: +31-20-4442816

Publication History

  1. Issue published online: 7 NOV 2008
  2. Article first published online: 16 OCT 2008
  3. Manuscript Accepted: 20 AUG 2008
  4. Manuscript Revised: 13 AUG 2008
  5. Manuscript Received: 3 APR 2008

Funded by

  • VUmc Institute for Cancer and Immunology (V-ICI), Amsterdam

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Keywords:

  • Allergy;
  • Chemotaxis;
  • Cytokines;
  • DC;
  • Skin

Abstract

The initial step in Langerhans cell (LC) migration from the epidermis to the lymph node involves migration of maturing LC into the dermis. Here, we investigated the migration of LC out of the epidermis after exposure of the skin to contact allergens. Ex vivo intact human skin, epidermal sheets, and LC derived from the MUTZ-3 cell line (MUTZ-LC) were used to determine whether dermal fibroblasts play a role in mediating LC migration towards the dermis. Exposure of epidermal sheets or MUTZ-LC to allergens (nickel sulphate, 2,4-dinitrochlorobenzene, and cinnamaldehyde) or a cytokine maturation cocktail resulted in LC migration towards dermal fibroblasts. This was due to upregulation of CXCR4 on maturing LC and secretion of CXCL12/stromal derived factor-1 chemokine by fibroblasts. Neutralizing antibodies to either CXCL12 or CXCR4 completely blocked migration. Injection of CXCL12 neutralizing antibodies into intact human skin totally inhibited LC migration into the dermis. In contrast, neutralizing antibodies to CCL19/CCL21 did not inhibit migration into the dermis. We describe a novel and essential role of dermis-derived CXCL12 in initiating migration of maturing human LC to the dermis thus permitting their further journey to the draining lymph nodes.

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