Induction of Il-17+ T Cell Trafficking and Development by Ifn-: Mechanism and Pathological Relevance in Psoriasis

Kryczek, I.; Bruce, A.T.; Gudjonsson, J.E.; Johnston, A.; Aphale, A.; Vatan, L.; Szeliga, W.; Wang, Y.; Liu, Y.; Welling, T.H.; Elder, J.T.; Zou, W.

The Journal of Immunology 181(7): 4733-4741

2008


DOI: 10.4049/jimmunol.181.7.4733
Accession: 068491173

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Abstract
Th1 and Th17 T cells are often colocalized in pathological environments, yet Th1-derived IFN-gamma inhibits Th17 cell development in vitro. We explored the physiologic basis of this paradox in humans. In this study, we demonstrate increased the number of CD4(+) and CD8(+) IL-17(+) T cells in skin lesions of psoriasis. Furthermore, we show that myeloid APCs potently support induction of IL-17(+) T cells, and that this activity is greatly increased in psoriasis. We tested stimuli that might account for this activity. Th1 cells and IFN-gamma are increased in psoriatic blood and lesional skin. We show that IFN-gamma programs myeloid APCs to induce human IL-17(+) T cells via IL-1 and IL-23. IFN-gamma also stimulates APC production of CCL20, supporting migration of IL-17(+) T cells, and synergizes with IL-17 in the production of human beta-defensin 2, an antimicrobial and chemotactic protein highly overexpressed by psoriatic keratinocytes. This study reveals a novel mechanistic interaction between Th1 and IL-17(+) T cells, challenges the view that Th1 cells suppress Th17 development through IFN-gamma, and suggests that Th1 and IL-17(+) T cells may collaboratively contribute to human autoimmune diseases.