IL-27 Facilitates Skin Wound Healing through Induction of Epidermal Proliferation and Host Defense.

IL-27 Facilitates Skin Wound Healing through Induction of Epidermal Proliferation and Host Defense.
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IL-27 通过诱导表皮增殖和宿主防御促进皮肤伤口愈合。

DOI:
10.1016/j.jid.2017.01.010
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发表时间:
2017-05
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
MacLeod AS
MacLeod AS
中科院分区:
其他
文献类型:
--
作者:
Yang B;Suwanpradid J;Sanchez-Lagunes R;Choi HW;Hoang P;Wang D;Abraham SN;MacLeod AS

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皮肤创伤修复需要上皮细胞增殖和分化以及抵抗入侵微生物的协调程序。然而,在这种炎症过程中触发上皮细胞增殖的因素还不完全清楚。在这项研究中,我们证明,IL-27是快速和短暂的CD 301 b+细胞在皮肤损伤后产生。IL-27和CD 301 b+细胞的功能作用通过以下发现得到证实:CD 301 b耗尽的小鼠在体内表现出延迟的伤口闭合,这可以通过局部IL-27治疗来挽救。此外,IL-27受体(Il 27 Ra −/−)的基因消融会减弱伤口愈合,这表明IL-27信号在体内皮肤再生中起着重要作用。从机制上讲,IL-27反馈角质形成细胞以刺激皮肤中的细胞增殖和再上皮化,而IL-27导致角质形成细胞终末分化的抑制。最后,我们确定IL-27有效地增加抗病毒寡腺苷酸合成酶2的表达,但不影响抗菌人β防御素2或再生胰岛衍生蛋白3-α的表达。总之,我们的数据表明IL-27在正常伤口愈合反应期间调节上皮细胞增殖和抗病毒宿主防御中的先前未被认识的作用。
Skin wound repair requires a coordinated program of epithelial cell proliferation and differentiation as well as resistance to invading microbes. However, the factors that trigger epithelial cell proliferation in this inflammatory process are incompletely understood. In this study, we demonstrate that IL-27 is rapidly and transiently produced by CD301b+ cells in the skin after injury. The functional role of IL-27 and CD301b+ cells is demonstrated by the finding that CD301b-depleted mice exhibit delayed wound closure in vivo, which could be rescued by topical IL-27 treatment. Furthermore, genetic ablation of the IL-27 receptor (Il27Ra−/−) attenuates wound healing, suggesting an essential role for IL-27 signaling in skin regeneration in vivo. Mechanistically, IL-27 feeds back on keratinocytes to stimulate cell proliferation and re-epithelialization in the skin, whereas IL-27 leads to suppression of keratinocyte terminal differentiation. Finally, we identify that IL-27 potently increases expression of the antiviral oligoadenylate synthetase 2, but does not affect expression of antibacterial human beta defensin 2 or regenerating islet-derived protein 3-alpha. Together, our data suggest a previously unrecognized role for IL-27 in regulating epithelial cell proliferation and antiviral host defense during the normal wound healing response.
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