The cytokine environment influence on human skin‐derived T cells

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 (T h )9–promoting condition (T h 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 T h 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.

Functional Interplay between IL-9 and Peptide YY Contributes to Chronic Skin Inflammation

“…Extensive studies have revealed that chronic inflammatory dermatoses are characterized by unfavorable keratinocyte proliferation and differentiation. As a central player of persistent skin inflammation, IL-9 has also been implicated in the pathogenesis of psoriasis and other inflammatory skin diseases (Baeck et al, 2018;Gutin et al, 2016;Hong et al, 2015;Kienzl et al, 2019;Ma et al, 2014;Midde et al, 2021;Ruiz-Romeu et al, 2018;Sismanopoulos et al, 2012). Studies in K14 CRE/ERT Il9ra ∆/∆ mice with inflammatory skin diseases clarified the functional significance of IL-9RA in keratinocytes during the development of corresponding skin lesions.…”

Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor PF-06700841 Reveal Reduction of Skin Inflammation in Plaque Psoriasis

“…The resident T cells are sustained at the site of inflammation by Jak1-and Jak3-dependent cytokines IL-2, IL-7, and IL-15 (Kienzl et al, 2019). Pathogenic Th17 T cells are triggered and sustained by IL-23 (Lee et al, 2012), which signals via TYK2/Jak2 (Lowes et al, 2013).…”

Network pharmacology and experiments in vitro reveal that the Paeonia veitchii Lynch and its active ingredient Punica granatum Linn ameliorate IMQ-induced psoriasis in mice via TLR4/NF-κB signaling pathway

“…CXCL8 receptors are found in keratinocytes of psoriatic lesions, and CXCL8 activates keratinocytes through autocrine secretion, and produces and releases in ammatory mediators, which contribute to the migration of neutrophils to the lesion site [18,19]. Some studies have shown that CXCL8 protein levels are positively correlated with PASI scores, further suggesting that CXCL8 may be closely related to the severity of psoriasis.…”