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NKG2D-dependent activation of dendritic epidermal T cells in contact hypersensitivity

Academic Article
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Overview

authors

  • Nielsen, M. M.
  • Dyring-Andersen, B.
  • Schmidt, J. D.
  • Witherden, D.
  • Lovato, P.
  • Woetmann, A.
  • Odum, N.
  • Poulsen, S. S.
  • Havran, Wendy
  • Geisler, C.
  • Bonefeld, C. M.

publication date

  • May 2015

journal

  • Journal of Investigative Dermatology  Journal

abstract

  • The interaction between keratinocytes (KCs) and skin-resident immune cells has an important role in induction of contact hypersensitivity. A specific subset of γδ T cells termed dendritic epidermal T cells (DETCs) are located in mouse epidermis, and we have recently shown that DETCs become activated and produce IL-17 in an IL-1β-dependent manner during contact hypersensitivity. Various receptors on DETCs, including NKG2D, are involved in DETC responses against tumors and during wound healing. The ligands for NKG2D (NKG2DL) are stress-induced proteins such as mouse UL16-binding protein-like transcript 1 (Mult-1), histocompatibility 60 (H60), and retinoic acid early inducible-1 (Rae-1) in mice and major histocompatibility complex (MHC) class I-chain-related A (MICA), MHC class I-chain-related B, and UL16-binding protein in humans. Here, we show that allergens upregulate expression of the NKG2DL Mult-1, H60, and Rae-1 in cultured mouse KCs and of MICA in primary human KCs. We demonstrate that Mult-1 is expressed in mouse skin exposed to allergen. Furthermore, we find that the vast majority of DETCs in murine epidermis and skin-homing cutaneous lymphocyte-associated antigen positive γδ T cells in humans express NKG2D. Finally, we demonstrate that blocking of NKG2D partially inhibits allergen-induced DETC activation. These findings demonstrate that NKG2D and NKG2DL are involved in allergen-induced activation of DETCs and indicate that the NKG2D/NKG2DL pathway might be a potential target for treatment of contact hypersensitivity.

subject areas

  • Allergens
  • Animals
  • Antibodies, Anti-Idiotypic
  • Carrier Proteins
  • Cell Line
  • Cells, Cultured
  • Dermatitis, Contact
  • Disease Models, Animal
  • Female
  • Histocompatibility Antigens Class I
  • Humans
  • Keratinocytes
  • Langerhans Cells
  • Mice
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily K
  • Nuclear Matrix-Associated Proteins
  • Nucleocytoplasmic Transport Proteins
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Identity

PubMed Central ID

  • PMC4402141

International Standard Serial Number (ISSN)

  • 0022-202X

Digital Object Identifier (DOI)

  • 10.1038/jid.2015.23

PubMed ID

  • 25634359
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Additional Document Info

start page

  • 1311

end page

  • 1319

volume

  • 135

issue

  • 5

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