IL-17 and IFN-gamma Mediate the Elicitation of Contact Hypersensitivity Responses by Different Mechanisms and Both Are Required for Optimal Responses

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2009 Jun 26

PMID 19553527

Citations 52

Authors

Donggou He

Lizhi Wu

Hee Kyung Kim

Hui Li

Craig A Elmets

Hui Xu

Affiliations

Soon will be listed here.

Abstract

Hapten-induced contact hypersensitivity (CHS) in the skin is a delayed type cellular immune response that can be mediated by CD8(+) T cells that produce IFN-gamma or IL-17. However, mechanisms for these cytokines in the elicitation of CHS remain to be fully elucidated. In this study, we show that adoptive transfer of CHS with hapten-primed wild-type (WT) CD8(+) T cells is reduced in IFN-gammaR(-/-) or IL-17R(-/-) mice compared with WT controls. The infiltration of granulocytes and macrophages in the hapten challenged skin of IL-17R(-/-) recipients is significantly reduced whereas it is less affected in IFN-gammaR(-/-) recipients although CD8(+) T cell infiltration is inhibited in both recipients. In contrast, the activity of reactive oxidative species is significantly inhibited in IFN-gammaR(-/-) but is less affected in IL-17R(-/-) recipients. Further analysis reveals that the expression of chemokines and cytokines is differentially regulated in the hapten-challenged skin of IFN-gammaR(-/-) or IL-17R(-/-) recipients compared with WT controls. Interestingly, injection of rIL-17 in the skin induces inflammation with a high level of leukocyte infiltration whereas injection of IFN-gamma induces inflammation with a high level of reactive oxidative species. Moreover, neutralization of IL-17 in IFN-gammaR(-/-) or IFN-gamma in IL-17R(-/-) mice further suppresses the adoptive transfer of CHS by hapten-primed WT CD8(+) T cells. The study demonstrates that IFN-gamma and IL-17 mediate the elicitation of CHS by different mechanisms and that both cytokines are required for optimal responses. This outcome improves understanding of pathogenesis and provides new insights into therapeutic strategies for CHS.

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