Altered expression of intracellular Toll-like receptors in peripheral blood mononuclear cells from patients with alopecia areata

Abdullateef A. Alzolibani , Zafar Rasheed , Ghada Bin Saif , Mohammed S. Al-Dhubaibi , Ahmad A. Al Robaee
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引用次数: 13

Abstract

Background

Toll-like receptors (TLRs) are pattern-recognition-receptors that sense a variety of pathogens and initiation of innate and adaptive immune responses. This study was undertaken to investigate the expression of TLRs in peripheral blood-mononuclear cells (PBMCs) of AA patients and to determine whether TLR-mediated inflammatory signals are important for the perspective of AA management.

Methods

Gene expression of TLRs and T-helper (Th) type-1, Th-2, Th-17 and regulatory T-cell cytokines in PBMCs was quantified by TaqMan Assays. Production of these cytokines in serum samples was determined by sandwich ELISAs.

Results

All TLRs (TLRs 1–10) were expressed in PBMCs of AA patients. Importantly intracellular TLRs (TLRs 3, 7, 8 and 9) were significantly up-regulated in AA patients as compared with controls (p < 0.05). Interleukin (IL)-2, TNF-α, and IL-17A gene expression in patients' PBMCs and their secretion in patients' sera were significantly higher as compared with their respective controls (p < 0.05). Whereas, TGF-β gene expression in patients' PBMCs and TGF-β protein level in patients' sera were significantly lower as compared with their controls (p < 0.05).

Conclusion

This is the first report that shows the comprehensive expression profile of TLRs in AA patients. We conclude that up-regulated expression of intracellular TLRs in PBMCs of AA patients may play an active role in abnormal regulation of Th-1, Th-17 and regulatory T-cell cytokines in alopecia areata.

General significance

Targeting of TLRs and their associated inflammatory signaling will open new areas of research; this may lead to the development of novel therapeutic targets for the treatment of AA or other skin disorders.

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斑秃患者外周血单个核细胞细胞内toll样受体表达的改变
toll样受体(TLRs)是一种模式识别受体,可感知多种病原体并启动先天和适应性免疫反应。本研究旨在探讨tlr在AA患者外周血单个核细胞(PBMCs)中的表达,并确定tlr介导的炎症信号是否对AA治疗有重要意义。方法采用TaqMan法测定PBMCs中TLRs、辅助性t细胞(Th) 1型、Th-2型、Th-17型及调节性t细胞因子的基因表达。用夹心elisa法测定血清样品中这些细胞因子的产生。结果所有TLRs (TLRs 1-10)均在AA患者外周血中表达。重要的是,与对照组相比,AA患者细胞内TLRs (TLRs 3、7、8和9)显著上调(p <0.05)。患者外周血中白细胞介素(IL)-2、TNF-α、IL- 17a基因表达及血清分泌均显著高于对照组(p <0.05)。与对照组相比,患者外周血中TGF-β基因表达及血清中TGF-β蛋白水平显著降低(p <0.05)。结论首次报道了AA患者中TLRs的全面表达谱。我们认为AA患者PBMCs细胞内TLRs表达上调可能在斑秃Th-1、Th-17及调节性t细胞因子异常调节中发挥积极作用。对tlr及其相关炎症信号的靶向研究将开辟新的研究领域;这可能会导致新的治疗靶点的发展,以治疗AA或其他皮肤疾病。
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