The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform

Prisco Mirandola - One of the best experts on this subject based on the ideXlab platform.

  • pkce promotes human th17 differentiation implications in the Pathophysiology of Psoriasis
    European Journal of Immunology, 2018
    Co-Authors: Silvia Martini, Sergio Di ,nuzzo, Giulia Pozzi, Cecilia Carubbi, Elena Masselli, Daniela Galli, Antonio Banchini, Giuliana Gobbi, Marco Vitale, Prisco Mirandola
    Abstract:

    PKCe 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 PKCe takes part in autoimmunity, its role in the molecular Pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCe 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) PKCe 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) PKCe interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCe 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 PKCe as a potential target in Th17-mediated diseases.

Silvia Martini - One of the best experts on this subject based on the ideXlab platform.

  • pkce promotes human th17 differentiation implications in the Pathophysiology of Psoriasis
    European Journal of Immunology, 2018
    Co-Authors: Silvia Martini, Sergio Di ,nuzzo, Giulia Pozzi, Cecilia Carubbi, Elena Masselli, Daniela Galli, Antonio Banchini, Giuliana Gobbi, Marco Vitale, Prisco Mirandola
    Abstract:

    PKCe 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 PKCe takes part in autoimmunity, its role in the molecular Pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCe 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) PKCe 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) PKCe interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCe 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 PKCe as a potential target in Th17-mediated diseases.

Sergio Di ,nuzzo - One of the best experts on this subject based on the ideXlab platform.

  • pkce promotes human th17 differentiation implications in the Pathophysiology of Psoriasis
    European Journal of Immunology, 2018
    Co-Authors: Silvia Martini, Sergio Di ,nuzzo, Giulia Pozzi, Cecilia Carubbi, Elena Masselli, Daniela Galli, Antonio Banchini, Giuliana Gobbi, Marco Vitale, Prisco Mirandola
    Abstract:

    PKCe 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 PKCe takes part in autoimmunity, its role in the molecular Pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCe 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) PKCe 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) PKCe interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCe 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 PKCe as a potential target in Th17-mediated diseases.

  • PKCε promotes human Th17 differentiation: Implications in the Pathophysiology of Psoriasis
    2018
    Co-Authors: Martini Silvia, Pozzi Giulia, Carubbi Cecilia, Masselli Elena, Galli Daniela, Sergio Di ,nuzzo, Banchini Antonio, Gobbi Giuliana, Vitale Marco, Mirandola Prisco
    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

Mark Lebwohl - One of the best experts on this subject based on the ideXlab platform.

  • a human interleukin 12 23 monoclonal antibody for the treatment of Psoriasis
    The New England Journal of Medicine, 2007
    Co-Authors: Gerald G. Krueger, Craig L Leonardi, Newman Yeilding, Lisa T Dooley, Richard G. Langley, Cynthia Guzzo, Yuhua Wang, Mark Lebwohl
    Abstract:

    Background Skin-infiltrating lymphocytes expressing type 1 cytokines have been linked to the Pathophysiology of Psoriasis. We evaluated the safety and efficacy of a human interleukin-12/23 monoclonal antibody in treating Psoriasis. Methods In this double-blind, placebo-controlled trial, 320 patients with moderate-to-severe plaque Psoriasis underwent randomization to treatment with the interleukin-12/23 monoclonal antibody (one 45-mg dose, one 90-mg dose, four weekly 45-mg doses, or four weekly 90-mg doses) or placebo; 64 patients were randomly assigned to each group. Patients assigned to the interleukin-12/23 monoclonal antibody received one additional dose at week 16 if needed. Patients assigned to placebo crossed over to receive one 90-mg dose of interleukin-12/23 monoclonal antibody at week 20. Results There was at least 75% improvement in the Psoriasis area-and-severity index at week 12 (the primary end point) in 52% of patients who received 45 mg of the interleukin-12/23 monoclonal antibody, in 59% o...

Fujio Otsuka - One of the best experts on this subject based on the ideXlab platform.

  • pituitary tumor transforming gene 1 induces tumor necrosis factor α production from keratinocytes implication for involvement in the Pathophysiology of Psoriasis
    Journal of Investigative Dermatology, 2013
    Co-Authors: Yosuke Ishitsuka, Yasuhiro Kawachi, Hiroshi Maruyama, Yasuhiro Fujisawa, Shijima Taguchi, Junichi Furuta, Yasuhiro Nakamura, Yoshiyuki Ishii, Fujio Otsuka
    Abstract:

    Proliferation and differentiation in the epidermis must be tightly regulated. This regulation is known to involve a range of transcription factors, including pituitary tumor transforming gene 1 (PTTG1), a ubiquitously distributed transcription factor that regulates keratinocyte proliferation and differentiation. Psoriasis is a common but refractory skin disorder, the Pathophysiology of which is characterized by hyperproliferation and impaired differentiation in the epidermis. The present study was conducted to clarify the less well-known roles of PTTG1 in the Pathophysiology of Psoriasis, focusing on its relationship with tumor necrosis factor-α (TNF-α), which is a critical mediator of the disease. The levels of PTTG1 expression were increased in the psoriatic epidermis. Overexpression of PTTG1 resulted in the overproduction of TNF-α, and TNF-α itself had an inductive effect on PTTG1 expression, suggesting that their expression may involve autoinduction. Moreover, overexpression of PTTG1 involved augmented the expression of cyclin A and B1 proteins in both cultured keratinocytes and the psoriatic epidermis. Therefore, enhanced expression of PTTG1 in the psoriatic epidermis may result in aberrant regulation of the cell cycle and impaired differentiation via the interplay between PTTG1 and TNF-α.

  • Transcription factor PTTG1 modulates growth and cytokine production of keratinocytes: Implication in the Pathophysiology of Psoriasis
    Journal of Dermatological Science, 2013
    Co-Authors: Yosuke Ishitsuka, Yasuhiro Kawachi, Hiroshi Maruyama, Yasuhiro Fujisawa, Shijima Taguchi, Junichi Furuta, Yasuhiro Nakamura, Yoshiyuki Ishii, Fujio Otsuka
    Abstract:

    f mitochondria in keratinization remains obscure. This study nvestigates whether mitochondria are associated with epideral keratinization. Mitochondrial distributionwas not observed to iffer by position in the epidermis, according to staining of mitohondrial outermembrane-locatedprotein (Tom20):Mitochondria ere mainly located in the perinuclear region of the cytoplasm. lectromicroscopic observation showednodifference ofmitochonrial morphology among basal, squamous and granular layers. owever, the expression patterns ofMfn1 andMfn2were quite diferent: Mfn1 was expressed in suprabasal keratinocytes, whereas fn2 was expressed only in basal keratinocytes. Both Mfn1 and fn2 were located in the perinuclear region of keratinocytes. Drp1 nd OPA1 expression in the keratinocytes was low. These results rovide novel evidence that Mfn1 and Mfn2 might be involved n the human epidermal keratinization process. It is possible that itochondrial fusion/fission is important to the cornification proess.