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CD39 is the dominant Langerhans cell–associated ecto-NTPDase: Modulatory roles in inflammation and immune responsiveness

Nature Medicine volume 8, pages 358–365 (2002)Cite this article

Abstract

CD39, the endothelial ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), regulates vascular inflammation and thrombosis by hydrolyzing ATP and ADP. Although ecto-NTPDase activities have been used as a marker of epidermal dendritic cells (DCs) known as Langerhans cells, the identity and function of these activities remain unknown. Here we report that Langerhans cells in CD39−/− mice express no detectable ecto-NTPDase activity. Irritant chemicals triggered rapid ATP and ADP release from keratinocytes and caused exacerbated skin inflammation in CD39−/− mice. Paradoxically, T cell–mediated allergic contact hypersensitivity was severely attenuated in CD39−/− mice. As to mechanisms, T cells increased pericellular ATP concentrations upon activation, and CD39−/− DCs showed ATP unresponsiveness (secondary to P2-receptor desensitization) and impaired antigen-presenting capacity. Our results show opposing outcomes of CD39 deficiency in irritant versus allergic contact dermatitis, reflecting its diverse roles in regulating extracellular nucleotide-mediated signaling in inflammatory responses to environmental insults and DC–T cell communication in antigen presentation.

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Figure 1: Lack of LC-associated ecto-NTPDase activities in CD39−/− mice.
Figure 2: CD39 mRNA and protein expression by LCs.
Figure 3: Nucleotide release from keratinocytes following in vitro treatment with skin-irritant chemicals.
Figure 4: Augmented skin inflammatory responses in CD39−/− mice.
Figure 5: Attenuated immune responses in CD39-deficient mice.
Figure 6: P2 receptor desensitization in CD39−/− DCs.

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Acknowledgements

We thank L. Ellinger, D. Edelbaum and P. Adcock for assistance. This work was supported by NIH grants (S.C.R. and A.T), the Dermatology Foundation fellowship award (N.M.), the Canadian Institutes of Health Research (J.S.), and the Centre de Recherches et d'Investigations Epidermiques et Sensorielles (CE.R.I.E.S.) award (A.T.).

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  1. Norikatsu Mizumoto and Tadashi Kumamoto: N.M. and T.K. contributed equally to this study.

Authors and Affiliations

  1. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Norikatsu Mizumoto, Tadashi Kumamoto, Hiroyuki Matsue & Akira Takashima

  2. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Simon C. Robson, Jean Sévigny & Keiichi Enjyoji

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  1. Norikatsu Mizumoto
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Correspondence to Akira Takashima.

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Mizumoto, N., Kumamoto, T., Robson, S. et al. CD39 is the dominant Langerhans cell–associated ecto-NTPDase: Modulatory roles in inflammation and immune responsiveness. Nat Med 8, 358–365 (2002). https://doi.org/10.1038/nm0402-358

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