IL-15 and IL-23 synergize to trigger Th17 response by CLA+ T cells in psoriasis.
Carmen de Jesús-GilEster Ruiz-RomeuMarta FerranMarc SagristàAnca ChiriacPablo GarcíaAntonio CeladaRamon M PujolLuis F Santamaria-BabíPublished in: Experimental dermatology (2020)
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.
Keyphrases
- systemic lupus erythematosus
- oxidative stress
- stem cells
- induced apoptosis
- transcription factor
- cell proliferation
- endothelial cells
- dna methylation
- single cell
- cell death
- cell therapy
- cell cycle arrest
- peritoneal dialysis
- copy number
- prognostic factors
- wound healing
- ankylosing spondylitis
- solid state
- patient reported outcomes