Psoriasis is a debilitating chronic skin disease with a worldwide prevalence. Its main features include well-marked silvery scales on the skin of hands and feet and back which arise due to hyperproliferation of keratinocytes and infiltration of immune cells in the skin. Multiple interactions exist between adaptive immune cells such as T cells and innate immune cells such as neutrophils and macrophages which are key players in the pathogenesis of psoriasis. Interleukin-2-inducible T-cell kinase (ITK) plays a key role in Th17 cell development through control of several transcription factors. ITK has been shown to control NFATc1, NFkB and STAT3 in CD4⁺ T cells. Effect of ITK inhibitor in imiquimod (IMQ)-induced psoriasiform inflammation remains to be explored. In the current examination, role of ITK signaling and its inhibition blockade were evaluated on NFATc1, NFkB and STAT3, IL-17A, TNF-α, IFN-γ, Foxp3, IL-10 in CD4⁺ T cells in IMQ model. Our data display that ITK signaling is involved in IMQ-induced psoriatic inflammation as paralleled by enhancement of p-ITK, NFATc1, p-NFkB and p-STAT3 in CD4⁺ T cells. It was associated with enhancement of Th17/Th1 cells and neutrophilic inflammation in the skin. Preventive treatment with ITK inhibitor led to a reduction in Th17/Th1 cells and enhancement of Treg cells. Overall, this study suggests that ITK signaling is an important modulator of transcription factor signaling in CD4⁺ T cells which is associated with Th17/Th1 cells and psoriasiform inflammation in mice. ITK signaling blockade could be a therapeutic target for the treatment of psoriatic inflammation.

牛皮癣是一种令人衰弱的慢性皮肤病，在世界范围内普遍流行。它的主要特征包括在手和脚和背部皮肤上明显标记的银色鳞片，这是由于角质形成细胞过度增殖和免疫细胞浸润在皮肤中而引起的。适应性免疫细胞（例如T细胞）与先天性免疫细胞（例如嗜中性粒细胞和巨噬细胞）之间存在多种相互作用，这是牛皮癣发病机理中的关键因素。白介素2诱导型T细胞激酶（ITK）通过控制几种转录因子在Th17细胞发育中起关键作用。已证明ITK可控制CD4 ^+中的NFATc1，NF k B和STAT3T细胞。ITK抑制剂在咪喹莫特（IMQ）诱导的牛皮癣样炎症中的作用仍有待探索。在当前的检查中，评估了IMQ模型中CD4 ⁺ T细胞中NFATc1，NF k B和STAT3，IL-17A，TNF-α，IFN-γ，Foxp3，IL-10对ITK信号的作用及其抑制阻断作用。我们的数据显示，ITK信号传导参与IMQ诱导的牛皮癣炎症，同时增强CD4 ^+中的p -ITK，NFATc1，p -NF k B和p -STAT3。T细胞。它与皮肤中Th17 / Th1细胞的增强和嗜中性粒细胞炎症有关。用ITK抑制剂进行预防性治疗可导致Th17 / Th1细胞减少，Treg细胞增强。总体而言，这项研究表明，ITK信号传导是CD4 ⁺ T细胞中转录因子信号传导的重要调节剂，与小鼠Th17 / Th1细胞和银屑病炎症有关。ITK信号传导阻断可能是银屑病炎症的治疗靶标。