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- Title
NKG2D-Dependent Activation of Dendritic Epidermal T Cells in Contact Hypersensitivity.
- Authors
Nielsen, Morten M; Dyring-Andersen, Beatrice; Schmidt, Jonas D; Witherden, Deborah; Lovato, Paola; Woetmann, Anders; Ødum, Niels; Poulsen, Steen S; Havran, Wendy L; Geisler, Carsten; Bonefeld, Charlotte M
- 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.
- Subjects
KILLER cells; DENDRITIC cells; T cells; ALLERGIES; KERATINOCYTES; IMMUNE response
- Publication
Journal of Investigative Dermatology, 2015, Vol 135, Issue 5, p1311
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2015.23