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

Publication ,  Journal Article
Nielsen, MM; Lovato, P; MacLeod, AS; Witherden, DA; Skov, L; Dyring-Andersen, B; Dabelsteen, S; Woetmann, A; Ødum, N; Havran, WL; Geisler, C ...
Published in: J Immunol
April 1, 2014

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.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2014

Volume

192

Issue

7

Start / End Page

2975 / 2983

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Skin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, gamma-delta
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Lymphocyte Activation
  • Langerhans Cells
  • Keratinocytes
 

Citation

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MLA
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Nielsen, M. M., Lovato, P., MacLeod, A. S., Witherden, D. A., Skov, L., Dyring-Andersen, B., … Bonefeld, C. M. (2014). IL-1β-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Immunol, 192(7), 2975–2983. https://doi.org/10.4049/jimmunol.1301689
Nielsen, Morten M., Paola Lovato, Amanda S. MacLeod, Deborah A. Witherden, Lone Skov, Beatrice Dyring-Andersen, Sally Dabelsteen, et al. “IL-1β-dependent activation of dendritic epidermal T cells in contact hypersensitivity.J Immunol 192, no. 7 (April 1, 2014): 2975–83. https://doi.org/10.4049/jimmunol.1301689.
Nielsen MM, Lovato P, MacLeod AS, Witherden DA, Skov L, Dyring-Andersen B, et al. IL-1β-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Immunol. 2014 Apr 1;192(7):2975–83.
Nielsen, Morten M., et al. “IL-1β-dependent activation of dendritic epidermal T cells in contact hypersensitivity.J Immunol, vol. 192, no. 7, Apr. 2014, pp. 2975–83. Pubmed, doi:10.4049/jimmunol.1301689.
Nielsen MM, Lovato P, MacLeod AS, Witherden DA, Skov L, Dyring-Andersen B, Dabelsteen S, Woetmann A, Ødum N, Havran WL, Geisler C, Bonefeld CM. IL-1β-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Immunol. 2014 Apr 1;192(7):2975–2983.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2014

Volume

192

Issue

7

Start / End Page

2975 / 2983

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Skin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, gamma-delta
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Lymphocyte Activation
  • Langerhans Cells
  • Keratinocytes