Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack
Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack
复制标题
DOI：
10.1038/sj.jid.5701183
复制
发表时间：
2008-05-01
影响因子：
6.5
通讯作者：
Paus, Ralf
中科院分区：
文献类型：
--
作者：
Ito, Taisuke;Ito, Natsuho;Paus, Ralf
毛囊（HFs）具有相对免疫特权（IP），其特征是主要组织相容性复合体（MHC） I类下调和强效免疫抑制剂的局部表达。正常情况下，自然杀伤细胞（NK）攻击MHC I类表达缺失或低表达的细胞。然而，由于在健康的人类生长原HFs周围很少发现滤泡周围NK细胞，我们想知道HFs是如何逃脱NK细胞攻击的。这项研究表明，这是通过活性NK细胞抑制发生的。相比之下，斑秃（AA），一种器官特异性自身免疫性疾病，被认为是由HF-IP崩溃引起的，在NK细胞抑制/遏制方面表现出明显的缺陷。我们发现NK细胞抑制剂巨噬细胞迁移抑制因子在HF上皮中强烈表达，与AA相比，在正常的生长原HF中和周围观察到很少的CD56(+)/NKG2D(+) NK细胞，而在AA-HF周围有明显的CD56(+)/NKG2D(+) NK细胞聚集。流式细胞术发现，健康对照组外周血CD56(+) NK细胞上NK功能激活受体（NKG2D、NKG2C）表达明显少于AA患者，而杀伤细胞igg样受体- 2d2 / 2d3表达明显多于AA患者。此外，与AA相比，在正常的生长原HFs中仅观察到MHC I类链相关A基因的弱免疫反应性。据我们所知，这一缺陷以前未被报道过，必须考虑到AA的发病机制和治疗。
Hair follicles (HFs) enjoy a relative immune privilege (IP) that is characterized by downregulation of major histocompatibility complex (MHC) class I and local expression of potent immunosuppressants. Normally, natural killer (NK) cells attack cells with absent/low MHC class I expression. However, because few perifollicular NK cells are found around healthy human anagen HFs, we asked how HFs escape from NK cell attack. This study suggests that this happens via an active NK cell suppression. Alopecia areata (AA), an organ-specific autoimmune disease thought to result from a collapse of HF-IP, in contrast, shows striking defects in NK cell inhibition/containment. We show that the NK cell inhibitor macrophage migration inhibitory factor is strongly expressed by the HF epithelium, and very few CD56(+)/NKG2D(+) NK cells are observed in and around normal anagen HFs compared to AA with prominent aggregations of CD56(+)/NKG2D(+) NK around AA-HFs. By flow cytometry, many fewer NK function-activating receptors (NKG2D, NKG2C) and significantly more killer cell Ig-like receptors-2D2/2D3 were found to be expressed on peripheral blood CD56(+) NK cells of healthy controls than on those of AA patients. In addition, only weak immunoreactivity for MHC class I chain-related A gene was observed in normal anagen HFs compared to AA. To our knowledge, this defect is previously unreported and must be taken into account in AA pathogenesis and its management.