Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (Alopecia Areata)
Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (Alopecia Areata)
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DOI：
10.1038/sj.jid.5700704
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发表时间：
2007-06-01
影响因子：
6.5
通讯作者：
Botchkarev, Vladimir A.
中科院分区：
文献类型：
--
作者：
Siebenhaar, Frank;Sharov, Andrey A.;Botchkarev, Vladimir A.
斑秃（AA）是一种毛囊自身免疫性疾病，其特征是活跃生长（生长期）毛囊周围的炎性细胞浸润。P物质（SP）在皮肤神经免疫网络中起关键作用，并通过神经激肽-1受体（NK-1 R）影响免疫细胞功能。为了更好地理解SP作为免疫调节神经肽在AA中的作用，我们研究了其在AA的C3 H/HeJ小鼠模型中的表达及其对免疫细胞的影响。在AA发展的早期阶段，与未受影响的小鼠相比，皮肤中SP免疫反应性神经纤维的数量增加。然而，在AA的晚期阶段，SP免疫反应神经的数量和SP蛋白水平在皮肤中减少，而SP降解酶中性内肽酶（NEP）的表达增加，与对照皮肤相比。在AA中，NK-1 R在受影响毛囊周围积聚的CD 8+淋巴细胞和巨噬细胞上表达。向AA受影响小鼠的皮肤供应额外的SP导致肥大细胞脱粒显著增加和毛囊退化加速（退化期），伴随着表达颗粒酶B的CD 8+细胞增加。这些数据表明，SP，NEP和NK-1 R作为重要的调节分子信号网络调节炎症反应的自身免疫性脱发。
Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss.