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Region Hovedstaden - en del af Københavns Universitetshospital
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IL-1β-dependent activation of dendritic epidermal T cells in contact hypersensitivity

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  • Morten M Nielsen
  • Paola Lovato
  • Amanda S MacLeod
  • Deborah A Witherden
  • Lone Skov
  • Beatrice Dyring-Andersen
  • Sally Dabelsteen
  • Anders Woetmann
  • Niels Ødum
  • Wendy L Havran
  • Carsten Geisler
  • Charlotte M Bonefeld
Vis graf over relationer

Substances that penetrate the skin surface can act as allergens and induce a T cell-mediated inflammatory skin disease called contact hypersensitivity (CHS). IL-17 is a key cytokine in CHS and was originally thought to be produced solely by CD4(+) T cells. However, it is now known that several cell types, including γδ T cells, can produce IL-17. In this study, we determine the role of γδ T cells, especially dendritic epidermal T cells (DETCs), in CHS. Using a well-established model for CHS in which 2,4-dinitrofluorobenzene (DNFB) is used as allergen, we found that γδ T cells are important players in CHS. Thus, more IL-17-producing DETCs appear in the skin following exposure to DNFB in wild-type mice, and DNFB-induced ear swelling is reduced by ∼50% in TCRδ(-/-) mice compared with wild-type mice. In accordance, DNFB-induced ear swelling was reduced by ∼50% in IL-17(-/-) mice. We show that DNFB triggers DETC activation and IL-1β production in the skin and that keratinocytes produce IL-1β when stimulated with DNFB. We find that DETCs activated in vitro by incubation with anti-CD3 and IL-1β produce IL-17. Importantly, we demonstrate that the IL-1R antagonist anakinra significantly reduces CHS responses, as measured by decreased ear swelling, inhibition of local DETC activation, and a reduction in the number of IL-17(+) γδ T cells and DETCs in the draining lymph nodes. Taken together, we show that DETCs become activated and produce IL-17 in an IL-1β-dependent manner during CHS, suggesting a key role for DETCs in CHS.

OriginalsprogEngelsk
TidsskriftJournal of immunology (Baltimore, Md. : 1950)
Vol/bind192
Udgave nummer7
Sider (fra-til)2975-83
Antal sider9
ISSN0022-1767
DOI
StatusUdgivet - 1 apr. 2014

ID: 44447913