PTHrP on MCF-7 breast cancer cells: a growth factor or an antimitogenic peptide?

Letter to the Edito

Apilimod Inhibits the Production of IL-12 and IL-23 and Reduces Dendritic Cell Infiltration in Psoriasis

Psoriasis is characterized by hyperplasia of the epidermis and infiltration of leukocytes into both the dermis and epidermis. IL-23, a key cytokine that induces TH17 cells, has been found to play a critical role in the pathogenesis of psoriasis. Apilimod is a small-molecule compound that selectively suppresses synthesis of IL-12 and IL-23. An open-label clinical study of oral administration of apilimod was conducted in patients with psoriasis. Substantial improvements in histology and clinical measurements were observed in patients receiving 70mg QD. The expression of IL-23p19 and IL-12/IL-23p40 in skin lesions was significantly reduced in this dose group, with a simultaneous increase in IL-10 observed. A decrease in the levels of TH1 and TH17 cytokines/chemokines in skin lesions followed these p19 and p40 changes. In parallel, a reduction in skin-infiltrating CD11c+ dendritic cells and CD3+ T cells was seen, with a greater decrease in the CD11c+ population. This was accompanied by increases in T and B cells, and decreases in neutrophils and eosinophils in the periphery. This study demonstrates the immunomodulatory activity of apilimod and provides clinical evidence supporting the inhibition of IL-12/IL-23 synthesis for the treatment of TH1- and TH17-mediated inflammatory diseases

The role of dendritic cells in the immunopathogenesis of psoriasis

Psoriasis vulgaris is a chronic inflammatory skin disease that is marked by a complex interplay of dendritic cells (DCs), T-cells, cytokines, and downstream transcription factors as part of a self-sustaining type 1 cytokine network. As integral players of the immune system, DCs represent antigen-presenting cells that are crucial for efficient activation of T-cells and B-cells. DCs have also been linked to distinct chronic inflammatory conditions, including psoriasis. In the setting of psoriasis therapy, DC/T cell interactions serve as a potential target for biologic response modifiers. Here we describe the major DC subsets as well as the immunologic involvement of DCs within the context of psoriatic lesions

Kinetics of circulating Th17 cytokines and adipokines in psoriasis patients

Psoriasis is associated with an increase of Th17 cytokines, such as IL-17, IL-22, IL-21, and TNF-α, which are produced by Th17 cells. Adipokines are peptide hormones or cytokines secreted from adipose tissues and involved in the pathogenesis of metabolic syndrome (MS). Psoriasis patients have a high prevalence of the MS. In this study, we investigated the statistics of circulating Th17-related cytokines and adipokines in psoriasis patients. Our study identified the significant elevation of serum IL-6, IL-21, IL-22, and resistin levels in psoriasis patients. Increased serum levels of IL-22 and adiponectin were positively correlated with Psoriasis Area and Severity Index (PASI). In contrast, serum high molecular weight adiponectin levels were decreased in psoriasis and negatively correlated with PASI

Dyadic adjustment, family coping, body image, quality of life and psychological morbidity in patients with psoriasis and their partners

Background Psoriasis is an incurable and chronic disease that includes unpredictable periods of remission and relapse requiring long-term therapy. Purpose This paper focuses on the relationship among family coping, psychological morbidity, body image, dyadic adjustment and quality of life in psoriatic patients and their partners. Method One hundred and one patients with psoriasis and 78 partners comprised the sample. They were regular users of the Dermatology Service of a Central Northern hospital in Portugal and a private dermatology clinic. Patients with psoriasis were assessed on anxiety, depression, body image, quality of life, dyadic adjustment and family coping. Partners were assessed on the same measures except body image and quality of life. Results A positive relationship among dyadic adjustment, psychological morbidity and family coping in patients and their partners was found. Also, patients with lower levels of quality of life had partners with higher levels of depressive and anxious symptoms. Better dyadic adjustment predicted family coping in the psoriatic patient. High levels of dyadic adjustment in patients and low partners’ trait anxiety predicted better dyadic adjustment in partners. Conclusion The results highlight the importance of incorporating family variables in psychological interventions in psoriasis’ care, particularly family coping and dyadic adjustment as well as the need for psychological intervention to focus both on patients and partners

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

Dendritic Cells as Danger-Recognizing Biosensors

Dendritic cells (DCs) are antigen presenting cells that are characterized by a potent capacity to initiate immune responses. DCs comprise several subsets with distinct phenotypes. After sensing any danger(s) to the host via their innate immune receptors such as Toll-like receptors, DCs become mature and subsequently present antigens to CD4+ T cells. Since DCs possess the intrinsic capacity to polarize CD4+ helper cells, it is critical to understand the immunological roles of DCs for clinical applications. Here, we review the different DC subsets, their danger-sensing receptors and immunological functions. Furthermore, the cytokine reporter mouse model for studying DC activation is introduced