The cytokine environment influence on human skin‐derived T cells. Issue 5 (26th February 2019) - Kienzl, Philip
ABSTRACT: Skin resident T cells provide immediate immunologic responses at their specific location and play a role in the pathogenesis of skin diseases such as psoriasis. Recently, IL‐9‐producing T cells were described as a major T‐cell subtype present in the skin, but knowledge on the biology and in situ regulation of this T‐cell subtype is scarce. Here, we investigated the cytokine influence on skin T cells with focus on IL‐9–producing T cells because a better understanding of their biology may identify novel therapeutic approaches. Healthy human skin biopsies were cultured either in the presence of IL‐2, IL‐4, and TGF‐β [T helper (Th )9–promoting condition (Th 9‐PC)] or IL‐2 and IL‐15 [standard condition (SC)]. Paired analysis of enzymatically isolated skin T cells and emigrated T cells after 4 wk of skin culture showed significant alterations of T‐cell phenotypes, cytokine production, and IL‐9‐producing T‐cell frequency. RNA sequencing analysis revealed differentially regulated pathways and identified CXCL8 and CXCL13 as top up‐regulated genes in Th 9‐PC compared with SC. Functionally supernatant of stimulated skin‐derived T cells, CXCL8 and CXCL13 increased neutrophil survival. We report that the cytokine environment alters skin‐derived T‐cell phenotype and functional properties.—Kienzl, P., Polacek, R., Reithofer, M., Reitermaier, R., Hagenbach, P., Tajpara, P., Vierhapper, M., Gschwandtner, M., Mildner, M. Jahn‐Schmid, B., Elbe‐Bürger, A. The cytokine environment influence on human skin–derived T cells. FASEB J. 33, 6514–6525 (2019). www.fasebj.org