Induction of IL-17+ T cell trafficking and development by IFN-γ: mechanism and pathological relevance in psoriasis

I Kryczek, AT Bruce, JE Gudjonsson… - The Journal of …, 2008 - journals.aai.org
I Kryczek, AT Bruce, JE Gudjonsson, A Johnston, A Aphale, L Vatan, W Szeliga, Y Wang…
The Journal of Immunology, 2008journals.aai.org
Th1 and Th17 T cells are often colocalized in pathological environments, yet Th1-derived
IFN-γ 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-γ are increased in …
Abstract
Th1 and Th17 T cells are often colocalized in pathological environments, yet Th1-derived IFN-γ 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-γ are increased in psoriatic blood and lesional skin. We show that IFN-γ programs myeloid APCs to induce human IL-17+ T cells via IL-1 and IL-23. IFN-γ also stimulates APC production of CCL20, supporting migration of IL-17+ T cells, and synergizes with IL-17 in the production of human β-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-γ, and suggests that Th1 and IL-17+ T cells may collaboratively contribute to human autoimmune diseases.
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