No abstract

No abstract

IL-9 is present in psoriatic lesions and is produced by lymphocytes. However, it is not known whether this cytokine is induced by relevant pathogenic triggers of psoriasis, such as Streptococcus pyogenes. Here we addressed the production of IL-9 in response to various pathogens in a psoriatic ex vivo model. Extracts of S. pyogenes and Candida albicans triggered the production of IL-9 and also IL-17A and IFN-γ. This induction was dependent on the interaction between CLA T cells and epidermal cells. Neutralization of IL-9 reduced S. pyogenes-induced IL-17A production by CLA T cells but had no effect on IFN-γ production. Also, IL-9 increased the survival of circulating psoriatic CLA T cells. Co-cultures from patients with guttate or plaque psoriasis with S. pyogenes produced similar amounts of IL-9. High cytokine responses in streptococcal-driven guttate patients paralleled peaks in Psoriasis Area Severity Index and anti-streptolysin O levels. Our results confirm that IL-9 promotes inflammation in psoriasis by up-regulating IL-17A production and support the clinical association of the immune response by streptococcal-sensitized CLA T cells with this cytokine, especially in guttate psoriasis.

IL‐15 has emerged as a potentially relevant target in the IL‐17 response in psoriasis. However, its mechanism is poorly characterized in humans. IL‐15 and IL‐23 are constitutively expressed in the psoriatic lesion. Also, IL‐15 is considered a susceptibility‐associated gene in psoriasis, as are IL‐23R, and HLACW6. Here, we studied the effect of IL‐15 and IL‐23 stimulation on the cytokine response of CLA+/CLA‐ T cells from 9 psoriasis patients and 3 healthy control subjects. To this end, CLA + and CLA‐ T cells from blood samples were cultured with epidermal cells from skin biopsies and treated with IL‐15 and IL‐23. After five days of culture, cytokines in supernatant were measured by ELISA or fluorescent bead‐based immunoassay. There was a statistically significant increase in IL‐17F and IL‐17A production (P < .001) in cocultures of psoriasis skin‐homing CLA + T cells with epidermal cells when stimulated with IL‐15 and IL‐23, but this effect was not observed in the cells of healthy controls. Interestingly, this response was reduced by around 50 to 80% by blocking HLA class I and II molecules. Our results point to the synergic action of IL‐15 and IL‐23 selectively for CLA + cells in psoriasis, leading to the induction of Th17 cell‐related cytokines.