The Journal of Allergy and Clinical Immunology
Volume 122, Issue 1 , Pages 126-132.e1, July 2008

Tacrolimus and TGF-β act synergistically on the generation of Langerhans cells

  • Bartlomiej Kwiek, MD

      Affiliations

    • Department of Dermatology and Allergology, University of Bonn, Bonn, Germany
    • Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
    • These authors contributed equally to this work.
    • ,
  • Wen-Ming Peng, MSc

      Affiliations

    • Department of Dermatology and Allergology, University of Bonn, Bonn, Germany
    • These authors contributed equally to this work.
    • ,
  • Jean-Pierre Allam, MD

      Affiliations

    • Department of Dermatology and Allergology, University of Bonn, Bonn, Germany
    • ,
  • Andrzej Langner, MD

      Affiliations

    • Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
    • ,
  • Thomas Bieber, MD, PhD

      Affiliations

    • Department of Dermatology and Allergology, University of Bonn, Bonn, Germany
    • ,
  • Natalija Novak, MD

      Affiliations

    • Department of Dermatology and Allergology, University of Bonn, Bonn, Germany
    • Corresponding Author InformationReprint requests: Natalija Novak, MD, Department of Dermatology and Allergology, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.

Received 23 December 2007; received in revised form 24 April 2008; accepted 2 May 2008. published online 11 June 2008.

Background

The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites.

Objectives

The effects of tacrolimus and TGF-β1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated.

Methods

The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-β production of skin cells was analyzed.

Results

Tacrolimus and TGF-β1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-β receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased.

Conclusion

The synergism between TGF-β1 and tacrolimus leads to the generation of LCs, reduced expression of costimulatory and MHC II molecules, and reduced stimulatory activity. Shifting the balance of the dendritic cell population to LCs might be of major importance for the therapeutic effect of tacrolimus.

Key words: Langerhans cells, inflammatory dendritic epidermal cells, atopic dermatitis, TGF-β, tacrolimus, TGF-β receptor

Abbreviations used: AD, Atopic dermatitis, DC, Dendritic cell, IDEC, Inflammatory dendritic epidermal cell, LC, Langerhans cell, PE, Phycoerythrin, RFI, Relative fluorescence intensity

 

 Supported by grants from the German Research Council (SFB704 A4; DFG NO454/1-4 and DFG NO454/2-3), a BONFOR grant of the University of Bonn, and a research grant of the Fujisawa/Astellas Pharma GmbH. N.N. is supported by a Heisenberg-Professorship of the DFG NO454/3-1 and NO454/5-1. B.K. was supported by a BONFOR grant and an Otto-Braun-Falco Fellowship.

 Disclosure of potential conflict of interest: T. Bieber has received research support from Astellas. N. Novak is on the speakers' bureau for Astellas. The rest of the authors report that they have no conflict of interest.

PII: S0091-6749(08)00939-1

doi:10.1016/j.jaci.2008.05.005

The Journal of Allergy and Clinical Immunology
Volume 122, Issue 1 , Pages 126-132.e1, July 2008

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