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IL-1 beta-dependent activation of dendritic epidermal T cells in contact hypersensitivity

Academic Article
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Overview

authors

  • Nielsen, M. M.
  • Lovato, P.
  • MacLeod, A. S.
  • Witherden, D. A.
  • Skov, L.
  • Dyring-Andersen, B.
  • Dabelsteen, S.
  • Woetmann, A.
  • Odum, N.
  • Havran, Wendy
  • Geisler, C.
  • Bonefeld, C. M.

publication date

  • April 2014

journal

  • Journal of Immunology  Journal

abstract

  • 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.

subject areas

  • Animals
  • Cell Line
  • Dermatitis, Contact
  • Dinitrofluorobenzene
  • Flow Cytometry
  • Gene Expression
  • Interleukin-17
  • Interleukin-1beta
  • Keratinocytes
  • Langerhans Cells
  • Lymphocyte Activation
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, gamma-delta
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin
  • T-Lymphocytes
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Identity

PubMed Central ID

  • PMC4020443

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1301689

PubMed ID

  • 24600030
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Additional Document Info

start page

  • 2975

end page

  • 2983

volume

  • 192

issue

  • 7

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