The effect of Interleukin-21 on the gene expression of psoriasis-associated chemokines in human keratinocyte cell line, HaCaT

Abstract

Psoriasis is a chronic inflammatory skin disease that affects approximately 1-3% of the population worldwide. In psoriasis, the stimulation of local innate immune response initiates inflammation, and in turn, initiates the adaptive immune response leading to the production of a panel of cytokines, chemokines and growth factors that eventually culminate in epidermal hyperplasia. Studies of recent have successfully linked the Interleukin (IL)-23⁄Th17 axis and keratinocytes, and have revealed that an increased expression of CCL20 from keratinocytes can recruit CCR6+ Th17 cells, and that the lesional cytokine milieu persistently activates keratinocytes to produce CCL20. IL-21, recently, has been found to play an important role in differentiation and function of T-cells. The production of IL-21 is mainly restricted to CD4+ T cells, Th17 and T-follicular helper (TFH) cells. In association to psoriasis, IL-21 was reported to be overexpressed in psoriatic skin and causes epidermal hyperplasia and inflammation when injected intradermally into mice.This study sought to clarify other effects of IL-21 in psoriasis, including its effect on the expression of psoriasis-related chemokines and antimicrobial peptides in keratinocytes, using microarray analysis and real time RT-PCR. Microarray analysis revealed statistically significant increase in the expression of CCL20 and CXCL8 upon keratinocyte stimulation with IL-21. Via real time quantitative PCR, we confirmed a significant increase in the expression of CCL20 and CXCL8 upon HaCaT stimulation with IL-21 – evidence supporting its role in the recruitment of Th17 cells and neutrophils to psoriatic skin. No change was observed in the expression of antimicrobial peptides upon IL-21 stimulation.We hope this further elucidation of the role of IL-21 aids in the advent of yet another potential therapeutic target in psoriasis.