Reduced skin homing by functional Treg in vitiligo.
Reduced skin homing by functional Treg in vitiligo.
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DOI：
10.1111/j.1755-148x.2010.00688.x
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发表时间：
2010-04
影响因子：
4.3
通讯作者：
Le Poole IC
中科院分区：
文献类型：
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作者：
Klarquist J;Denman CJ;Hernandez C;Wainwright DA;Strickland FM;Overbeck A;Mehrotra S;Nishimura MI;Le Poole IC
在人类白癜风中，皮肤色素脱失涉及自身反应性 T 细胞的细胞毒活性。据推测，在缺乏调节性 T 细胞 (Treg) 的情况下，色素脱失可能会发生。通过 CD3 和 FoxP3 免疫酶双染色评估皮肤浸润 T 细胞中 Treg 的百分比，结果显示非病变、病变周围和病变白癜风皮肤中 Treg 数量急剧减少。通过 FACS 分析 CD4、CD25、CD127 和 FoxP3 表达以及在存在和不存在分选 Treg 的情况下混合淋巴细胞反应对循环 Treg 池进行评估，发现白癜风患者中 Treg 的丰度或活性没有全身性下降。循环白癜风和对照 Treg 中皮肤归巢受体 CCR4、CCR5、CCR8 和 CLA 的表达相当。任一来源的 Treg 均能够向 CCR4 配体和皮肤归巢趋化因子 CCL22 迁移，但免疫组织化学观察到白癜风皮肤中 CCL22 表达显着降低，这可能解释了白癜风中循环功能性 Treg 未能归巢至皮肤的原因。白癜风皮肤中 Treg 的缺乏可能对于进展性疾病中持续的抗黑素细胞反应至关重要。
In human vitiligo, cutaneous depigmentation involves cytotoxic activity of autoreactive T cells. It was hypothesized that depigmentation can progress in the absence of regulatory T cells (Treg). The percentage of Treg among skin infiltrating T cells was evaluated by immunoenzymatic double staining for CD3 and FoxP3, revealing drastically reduced numbers of Treg in non-lesional, perilesional and lesional vitiligo skin. Assessment of the circulating Treg pool by FACS analysis of CD4, CD25, CD127 and FoxP3 expression, and mixed lymphocyte reactions in presence and absence of sorted Treg revealed no systemic drop in the abundance or activity of Treg in vitiligo patients. Expression of skin homing receptors CCR4, CCR5, CCR8 and CLA was comparable among circulating vitiligo and control Treg. Treg from either source were equally capable of migrating towards CCR4 ligand and skin homing chemokine CCL22, yet significantly reduced expression of CCL22 in vitiligo skin observed by immunohistochemistry may explain failure of circulating, functional Treg to home to the skin in vitiligo. The paucity of Treg in vitiligo skin is likely crucial for perpetual anti-melanocyte reactivity in progressive disease.