Possible involvement of type 2 cytokines in alloknesis in mouse models of menopause and dry skin
Possible involvement of type 2 cytokines in alloknesis in mouse models of menopause and dry skin
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DOI：
10.1111/exd.14422
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发表时间：
2021-07-03
影响因子：
3.6
通讯作者：
Katagiri, Kazumoto
中科院分区：
文献类型：
--
作者：
Ichimasu, Nao;Chen, Yue;Katagiri, Kazumoto
异感是一种由无害刺激引起的异常瘙痒感觉，是特应性皮炎患者瘙痒-抓挠恶性循环的关键现象。皮肤干燥和瘙痒，包括感觉异常，是绝经期和绝经后妇女的主要健康问题。我们最近报道了卵巢切除（OVX）小鼠的渗透屏障功能障碍，这是一种更年期模型，并发现这种功能障碍与皮肤干燥有关。然而，瘙痒的机制仍然未知。因此，我们研究了触摸和致敏原诱发的变感和表皮神经支配的OVX小鼠和丙酮，乙醚和水（AEW）处理的小鼠，实验性皮肤干燥模型。OVX和AEW小鼠的变感和表皮神经支配相当。针对IL-4和IL-13的中和抗体在皮内给药后30 min即可抑制OVX和AEW小鼠的变应性。在HRT和Sham小鼠以及AEW和对照小鼠的皮肤中发现接近IL-4测量限的可比值，但OVX小鼠的IL-4水平在测量限内。我们在任何组小鼠中均未检测到IL-4或IL-13的mRNA。另一方面，在OVX和AEW小鼠中嗜酸性粒细胞和嗜碱性粒细胞的数量增加。这些结果表明，受损的屏障功能与来源于皮肤中嗜酸性粒细胞和嗜碱性粒细胞的2型细胞因子或与内源性2型细胞因子合作可能触发变应性的发展，因此，这些细胞因子可能是敏感性皮肤的治疗靶点。
Alloknesis, an abnormal itch sensation induced by innocuous stimuli, is a key phenomenon in the vicious itch-scratch cycle in patients with atopic dermatitis. Dry skin and pruritus, including alloknesis, are major health problems in peri- and post-menopausal women. We recently reported permeability barrier dysfunction in ovariectomized (OVX) mice-a model of menopause-and found that the dysfunction was related to dry skin. However, the mechanism of the itch remains unknown. Therefore, we examined touch- and pruritogen-evoked alloknesis and epidermal innervation in OVX mice and acetone, diethyl ether and water (AEW)-treated mice, for the experimental dry skin model. Both alloknesis and epidermal innervation were comparable in OVX and AEW mice. Neutralizing antibodies against IL-4 and IL-13 inhibited alloknesis in both OVX and AEW mice as early as 30 min after intradermal administration. Comparable values close to the measurement limit of IL-4 were found in the skin of HRT and Sham mice as well as AEW and the control mice, but the levels of IL-4 were within the measurement limit in OVX mice. We could not detect mRNAs of IL-4 or IL-13 in any groups of mice. On the other hand, the number of eosinophils and basophils was increased in OVX and AEW mice. These results suggest that impaired barrier function in cooperation with type 2 cytokines derived from eosinophils and basophils in the skin or with endogenous type 2 cytokine may trigger the development of alloknesis, and thus, these cytokines could be a therapeutic target for sensitive skin.