IL-17R-EGFR axis links wound healing to tumorigenesis in Lrig1+ stem cells

被引：91

作者：

Chen, Xing ^{[1
]}

Cai, Gang ^{[1
,9
]}

Liu, Caini ^{[1
]}

Zhao, Junjie ^{[1
,2
]}

Gu, Chunfang ^{[1
,3
]}

Wu, Ling ^{[1
]}

Hamilton, Thomas A. ^{[1
]}

Zhang, Cun-Jin ^{[1
,4
]}

Ko, Jennifer ^{[5
]}

Zhu, Liang ^{[5
]}

Qin, Jun ^{[6
]}

Vidimos, Allison ^{[6
]}

Koyfman, Shlomo ^{[7
]}

Gastman, Brian R. ^{[1
,6
,8
]}

Jensen, Kim B. ^{[10
,11
]}

Li, Xiaoxia ^{[1
]}

机构：

[1] Cleveland Clin, Dept Inflammat & Immun, Cleveland, OH 44106 USA

[2] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA

[3] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA

[4] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA

[5] Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA

[6] Cleveland Clin, Dept Dermatol, Cleveland, OH 44106 USA

[7] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA

[8] Cleveland Clin, Dept Plast Surg, Cleveland, OH 44106 USA

[9] Shanghai Jiao Tong Univ, Sch Med, Dept Lab Med, Ruijin Hosp, Shanghai, Peoples R China

[10] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Stem Cell Res, Copenhagen, Denmark

[11] Univ Copenhagen, BRIC, Copenhagen, Denmark

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2019年 / 216卷 / 01期

基金：

美国国家卫生研究院;

关键词：

GROWTH-FACTOR RECEPTOR; SUBMAXILLARY GLAND; TUMOR INITIATION; PLAQUE PSORIASIS; ADAPTER PROTEIN; LIGAND-BINDING; MESSENGER-RNA; CUTTING EDGE; IN-VITRO; IL-17;

D O I：

10.1084/jem.20171849

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Lrig1 marks a distinct population of stem cells restricted to the upper pilosebaceous unit in normal epidermis. Here we report that IL-17A-mediated activation of EGFR plays a critical role in the expansion and migration of Lrig1(+) stem cells and their progenies in response to wounding, thereby promoting wound healing and skin tumorigenesis. Lrig1-specific deletion of the IL-17R adaptor Act1 or EGFR in mice impairs wound healing and reduces tumor formation. Mechanistically, IL-17R recruits EGFR for IL-17A-mediated signaling in Lrig1(+) stem cells. While TRAF4, enriched in Lrig1(+) stem cells, tethers IL-17RA and EGFR, Act1 recruits c-Src for IL-17A-induced EGFR transactivation and downstream activation of ERK5, which promotes the expansion and migration of Lrig1(+) stem cells. This study demonstrates that IL-17A activates the IL-17R-EGFR axis in Lrig1(+) stem cells linking wound healing to tumorigenesis.

引用

页码：195 / 214

页数：20

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