IL-1β–Dependent Activation of Dendritic Epidermal T Cells in Contact Hypersensitivity
- 1 April 2014
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 192 (7), 2975-2983
- https://doi.org/10.4049/jimmunol.1301689
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.Keywords
This publication has 37 references indexed in Scilit:
- Dendritic epidermal T cells regulate skin antimicrobial barrier functionJCI Insight, 2013
- Rorγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in miceJCI Insight, 2012
- Cutting Edge: Dendritic Epidermal γδ T Cell Ligands Are Rapidly and Locally Expressed by Keratinocytes following Cutaneous WoundingPublished by The American Association of Immunologists ,2012
- Pivotal Role of Dermal IL-17-Producing γδ T Cells in Skin InflammationImmunity, 2011
- Identification of a Novel Proinflammatory Human Skin-Homing Vγ9Vδ2 T Cell Subset with a Potential Role in PsoriasisThe Journal of Immunology, 2011
- Cutting Edge: Identification of a Motile IL-17–Producing γδ T Cell Population in the DermisThe Journal of Immunology, 2011
- Functions of skin-resident γδ T cellsCellular and Molecular Life Sciences, 2011
- Cutaneous immunosurveillance by self-renewing dermal γδ T cellsThe Journal of Experimental Medicine, 2011
- IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in miceJCI Insight, 2010
- Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitisBritish Journal of Dermatology, 2009