Immunity：REG3A调节银屑病和皮肤修复的细胞增殖和分化

上皮角质形成细胞增殖,是创面修复必不可少的因素，而上皮细胞增殖异常是皮肤疾病银屑病的内在原因。这些炎症过程中上皮细胞增殖的触发因子尚未完全理解。

本研究表明，再生性胰岛起源蛋白3α（REG3A）在银屑病、创面修复以及咪喹莫特诱导银屑病皮损情况下的角质细胞中高度表达。

研究还发现，白细胞介素17（IL-17）通过活化角质细胞编码的IL-17受体A（IL-17RA）诱导角质细胞表达。REG3A结合exostosin样3蛋白（EXTL3）进而激活磷酸肌醇3激酶（PI3K）和激酶Akt，从而抑制角质细胞的终末分化并增加细胞增殖。

这些研究结果显示，REG3A，一种肠道分泌的抗菌蛋白，能促进皮肤角质形成细胞增殖，并受IL-17诱导。这一研究表明，REG3A可能介导在正常创面修复和银屑病条件下的表皮增生。

doi:10.1016/j.cell.2011.10.017
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The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury

Yuping Lai, Dongqing Li, Changwei Li, Beda Muehleisen, Katherine A. Radek, Hyun Jeong Park, Ziwei Jiang, Zhiheng Li, Hu Lei, Yanchun Quan, Tian Zhang, Yelin Wu, Paul Kotol, Shin Morizane, Tissa R. Hata, Keiji Iwatsuki, Ce Tang, Richard L. Gallo

Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.