Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding

被引：269

作者：

Gay, Denise ^{[1
]}

Kwon, Ohsang ^{[1
,2
]}

Zhang, Zhikun ^{[1
]}

Spata, Michelle ^{[1
]}

Plikus, Maksim V. ^{[1
]}

Holler, Phillip D. ^{[1
]}

Ito, Mayumi ^{[3
]}

Yang, Zaixin ^{[1
]}

Treffeisen, Elsa ^{[1
]}

Kim, Chang D. ^{[4
]}

Nace, Arben ^{[1
]}

Zhang, Xiaohong ^{[1
]}

Baratono, Sheena ^{[1
]}

Wang, Fen ^{[5
]}

Ornitz, David M. ^{[6
]}

Millar, Sarah E. ^{[1
,7
]}

Cotsarelis, George ^{[1
]}

机构：

[1] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA

[2] Seoul Natl Univ, Coll Med, Dept Dermatol, Seoul, South Korea

[3] NYU, Dept Dermatol, Langone Med Ctr, New York, NY 10016 USA

[4] Chungnam Natl Univ, Sch Med, Dept Dermatol, Taejon, South Korea

[5] Texas A&M Univ, Hlth Sci Ctr, Inst Biosci & Technol, Ctr Canc Biol & Nutr, Houston, TX USA

[6] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA

[7] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA

来源：

NATURE MEDICINE | 2013年 / 19卷 / 07期

基金：

美国国家卫生研究院;

关键词：

NORMAL HUMAN-SKIN; BETA-CATENIN; GENE-EXPRESSION; MORPHOGENESIS; RESIDENT; RECEPTOR; GROWTH; REPAIR; IDENTIFICATION; REGENERATION;

D O I：

10.1038/nm.3181

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Understanding molecular mechanisms for regeneration of hair follicles provides new opportunities for developing treatments for hair loss and other skin disorders. Here we show that fibroblast growth factor 9 (Fgf9), initially secreted by gamma delta T cells, modulates hair follicle regeneration after wounding the skin of adult mice. Reducing Fgf9 expression decreases this wound-induced hair neogenesis (WIHN). Conversely, overexpression of Fgf9 results in a two-to threefold increase in the number of neogenic hair follicles. We found that Fgf9 from gamma delta T cells triggers Wnt expression and subsequent Wnt activation in wound fibroblasts. Through a unique feedback mechanism, activated fibroblasts then express Fgf9, thus amplifying Wnt activity throughout the wound dermis during a crucial phase of skin regeneration. Notably, humans lack a robust population of resident dermal gamma delta T cells, potentially explaining their inability to regenerate hair after wounding. These findings highlight the essential relationship between the immune system and tissue regeneration. The importance of Fgf9 in hair follicle regeneration suggests that it could be used therapeutically in humans.

引用

页码：916 / +

页数：9

共 38 条

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Delineation of the function of a major γδ T cell subset during infection [J].