PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4+-T cells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4+-T cells from patients with psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4+subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: (i) PKCε is overexpressed in CD4+-T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4+-T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases.

PKCε promotes human Th17 differentiation: Implications in the pathophysiology of psoriasis / Martini, Silvia; Pozzi, Giulia; Carubbi, Cecilia; Masselli, Elena; Galli, Daniela; Nuzzo, Sergio Di; Banchini, Antonio; Gobbi, Giuliana; Vitale, Marco; Mirandola, Prisco. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - 48:4(2018), pp. 644-654. [10.1002/eji.201747102]

PKCε promotes human Th17 differentiation: Implications in the pathophysiology of psoriasis

Martini, Silvia;Pozzi, Giulia;Carubbi, Cecilia;Masselli, Elena;Galli, Daniela;Nuzzo, Sergio Di;BANCHINI, ANTONIO;Gobbi, Giuliana;Vitale, Marco
;
Mirandola, Prisco
2018

Abstract

PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4+-T cells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4+-T cells from patients with psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4+subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: (i) PKCε is overexpressed in CD4+-T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4+-T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases.
PKCε promotes human Th17 differentiation: Implications in the pathophysiology of psoriasis / Martini, Silvia; Pozzi, Giulia; Carubbi, Cecilia; Masselli, Elena; Galli, Daniela; Nuzzo, Sergio Di; Banchini, Antonio; Gobbi, Giuliana; Vitale, Marco; Mirandola, Prisco. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - 48:4(2018), pp. 644-654. [10.1002/eji.201747102]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2839156
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