Department of Dermatology and Venereology, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, 110029, New Delhi, India.
Br J Dermatol. 2015 Apr;172(4):940-50. doi: 10.1111/bjd.13511. Epub 2015 Feb 27.
Vitiligo is an autoimmune depigmentation disease, and defects in regulatory T cells (Tregs) have been proposed in the pathogenesis of generalized vitiligo (GV). However, the role of programmed cell death (PD)1(+) Tregs has not been studied.
To investigate the status of Tregs, PD1(+) Tregs and associated parameters in active GV (aGV) during the first episode of disease attack and to establish the clinical correlation.
The percentages of circulating Tregs, PD1(+) Tregs and CD3(+) CD4(+) PD1(+) T cells were evaluated in 50 patients with aGV and 51 controls. Expression levels of FOXP3, TGFB1, CTLA4 and genes for chemokine receptors (CCR4, CCR7) and their ligands (CCL21, CCL22) were quantified in peripheral blood and in lesional, perilesional, nonlesional and normal skin sections. The corresponding proteins were immunolocalized in tissue of aGV.
The percentage of Tregs was decreased (P = 0·001) and that of PD1(+) Tregs increased (P = 0·001) in peripheral blood of patients with aGV compared with controls. The abundance of TGFB1 and CCL21 mRNA was significantly decreased in the peripheral blood of patients with aGV. Significant differences in forkhead box P3, transforming growth factor-β and CCL21 protein expression were found in skin sections.
Deficiency in Treg frequency and decreased expression of Treg-associated parameters (TGFB and CCL21) suggested a possible defect in Tregs that may alter their suppression function and skin homing in aGV. The increased PD1(+) Tregs suggests that the PD1/PD ligand pathway may be involved in aGV and may have a role in Treg exhaustion. Further study is required to delineate the effect of PD1 in regulating Treg function in aGV.
白癜风是一种自身免疫性脱色素疾病，人们提出调节性 T 细胞（Tregs）的缺陷可能与泛发性白癜风（GV）的发病机制有关。然而，PD-1（+）Tregs 的作用尚未得到研究。
在疾病首次发作时，研究活动期 GV（aGV）中循环 Tregs、PD1（+）Tregs 和相关参数的状态，并建立临床相关性。
评估 50 例 aGV 患者和 51 例对照者外周血中循环 Tregs、PD1（+）Tregs 和 CD3（+）CD4（+）PD1（+）T 细胞的比例。在外周血和皮损、皮损旁、非皮损和正常皮肤切片中定量检测 FOXP3、TGFB1、CTLA4 以及趋化因子受体（CCR4、CCR7）及其配体（CCL21、CCL22）的基因表达水平。在 aGV 组织中免疫定位相应的蛋白质。
与对照组相比，aGV 患者外周血中 Tregs 的比例降低（P=0·001），PD1（+）Tregs 的比例升高（P=0·001）。GV 患者外周血中 TGFB1 和 CCL21 mRNA 的丰度显著降低。在皮肤切片中发现 FOXP3、转化生长因子-β和 CCL21 蛋白表达有显著差异。
Treg 频率的降低和与 Treg 相关参数（TGFB 和 CCL21）的表达降低表明 Treg 可能存在缺陷，这可能改变它们在 aGV 中的抑制功能和皮肤归巢。PD1（+）Tregs 的增加表明 PD1/PD 配体通路可能参与 aGV，并可能在 Treg 耗竭中发挥作用。需要进一步研究以阐明 PD1 对调节 aGV 中 Treg 功能的影响。
