Dermal Vγ6+ γδ T17 Cells are Involved in Skin Pressure Ulcers in Mice
Dermal Vγ6+ γδ T17 Cells are Involved in Skin Pressure Ulcers in Mice
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真皮 Vγ6+ γδ T17 细胞参与小鼠皮肤压疮
DOI：
10.1016/j.jid.2021.12.030
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发表时间：
2022
影响因子：
6.5
通讯作者：
Yoshikai Yasunobu
中科院分区：
文献类型：
--
作者：
Mine Keiichiro;Tun Xin;Hatano Shinya;Noguchi Naoto;Iwakura Yoichiro;Sawa Shinichiro;Nagafuchi Seiho;Yoshikai Yasunobu
压力性溃疡，也称为褥疮或褥疮，是卧床不起的患者的慢性问题（Black等人，2007年）。溃疡的形成是由于反复循环的缺血-再灌注（IR）。IR诱导的皮肤溃疡和坏死导致瘢痕形成和炎症（Eming等人，2014年）。然而，迄今为止，压力性溃疡的免疫学方面仍不清楚。最近建立了压力性溃疡的小鼠模型（Stadler等人，2004年）。IL-17（也称为IL-17 A）表达水平在压力性溃疡中增加，表明IL-17可能与这些溃疡相关（Cui等人，2013年）。IL-17是一种T细胞衍生的促炎细胞因子，已显示其参与嗜中性粒细胞的动员（McGeachy等人，2019年）。TCR γδ和TCR αβ T细胞都能够产生IL-17。与在外周功能性分化为产生IL-17的效应细胞（T辅助细胞17）的αβ T细胞不同，具有能够产生IL-17的效应功能的γδ T细胞（γδ T17细胞）在早期胎儿胸腺中发育（柴田et al.，2008年）。在表达7种Vγ基因的γδ T细胞中，使用Heilig和Tonegawa（1986）的命名法，Vγ4+ γδ T细胞和Vγ6+ γδ T细胞是γδ T细胞中唯一的IL-17产生者。在感染和皮炎的小鼠模型中显示了γδ T17细胞的重要作用（Cai等人，2011; Dejima等人，2011年; Guo等人，2013; Murakami等人，2016;柴田等人，2007年）。我们最近开发了对鼠Vγ6链特异性的mAb，并发现在银屑病样皮炎期间Vγ6+ γδ T17细胞比Vγ4+ γδ T17细胞更占优势;此外，Vγ6+ γδ T细胞功能的沉默对于保护咪喹莫特诱导的皮肤炎症是有效的（Hatano et al.，2019年）。然而，γδ T17细胞在压疮中的作用仍不清楚。在这项研究中，我们使用小鼠IR模型研究了γδ T17细胞在压疮中的作用。
Pressure ulcers, also known as bedsore or decubitus, are a chronic problem for bedridden patients (Black et al., 2007). The formation of ulcers is due to repeated cycles of ischemia–reperfusion (IR). IR-induced skin ulceration and necrosis lead to scar formation and inflammation (Eming et al., 2014). However, to date, the immunological aspect of pressure ulcers remains unclear.A mouse model of pressure ulcers has recently been established (Stadler et al., 2004). IL-17 (also known as IL-17A) expression levels were increased in pressure ulcers, suggesting that IL-17 may be associated with these ulcers (Cui et al., 2013). IL-17 is a T cell-derived proinflammatory cytokine that has been shown to be involved in the mobilization of neutrophils (McGeachy et al., 2019). Both TCR γδ and TCR αβ T cells were able to produce IL-17. Unlike αβ T cells, which are functionally differentiated to IL-17–producing effector cells (T helper 17 cells) at the periphery, γδ T cells, with an effector function capable of producing IL-17 (γδ T17 cells), develop in the early fetal thymus (Shibata et al., 2008). Among γδ T cells expressing seven Vγ genes, using the nomenclature of Heilig and Tonegawa (1986), Vγ4+ γδ T cells and Vγ6+ γδ T cells are exclusive IL-17 producers among γδ T cells. Important roles of γδ T17 cells were shown in mouse models of infections and dermatitis (Cai et al., 2011; Dejima et al., 2011; Guo et al., 2013; Murakami et al., 2016; Shibata et al., 2007). We recently developed a mAb specific to the murine Vγ6 chain and found that Vγ6+ γδ T17 cells were more dominant than Vγ4+ γδ T17 cells during psoriasis-like dermatitis; moreover, silencing of the Vγ6+ γδ T cell function was effective for the protection of skin inflammation induced by imiquimod (Hatano et al., 2019). However, the contribution of γδ T17 cells in pressure ulcers remains unknown. In this study, we examined the role of γδ T17 cells in pressure ulcers using a mouse IR model.