Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin

被引:254
作者
Nagao, Keisuke [1 ]
Kobayashi, Tetsuro [1 ]
Moro, Kazuyo [2 ]
Ohyama, Manabu [1 ]
Adachi, Takeya [1 ]
Kitashima, Daniela Y. [1 ]
Ueha, Satoshi [3 ]
Horiuchi, Keisuke [4 ,5 ]
Tanizaki, Hideaki [6 ]
Kabashima, Kenji [6 ]
Kubo, Akiharu [1 ,5 ]
Cho, Young-hun [7 ]
Clausen, Bjorn E. [8 ]
Matsushima, Kouji [3 ]
Suematsu, Makoto [9 ,10 ]
Furtado, Glaucia C. [11 ]
Lira, Sergio A. [11 ]
Farber, Joshua M. [12 ]
Udey, Mark C. [7 ]
Amagai, Masayuki [1 ]
机构
[1] Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan
[2] RIKEN Res Ctr Allergy & Immunol, Lab Immune Cell Syst, Yokohama, Kanagawa, Japan
[3] Univ Tokyo, Dept Prevent Med, Tokyo, Japan
[4] Keio Univ, Sch Med, Dept Orthoped, Tokyo, Japan
[5] Keio Univ, Sch Med, Ctr Integrated Med Res, Tokyo, Japan
[6] Kyoto Univ, Fac Med, Dept Dermatol, Kyoto 606, Japan
[7] NCI, Dermatol Branch, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA
[8] Erasmus Univ, Dept Immunol, Med Ctr, NL-3000 DR Rotterdam, Netherlands
[9] Keio Univ, Sch Med, Dept Biochem, Tokyo, Japan
[10] Japan Sci & Technol Agcy, Exploratory Res Adv Technol, Suematsu Gas Biol Project, Tokyo, Japan
[11] Mt Sinai Sch Med, Inst Immunol, New York, NY USA
[12] NIAID, Lab Mol Immunol, US Natl Inst Hlth, Bethesda, MD 20892 USA
基金
日本学术振兴会;
关键词
LANGERHANS CELLS; LYMPHOCYTE EGRESS; IMMUNE-RESPONSE; STEM-CELLS; T-CELLS; BULGE; POPULATION; DISTINCT; MICE; SPHINGOSINE-1-PHOSPHATE;
D O I
10.1038/ni.2353
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Langerhans cells (LCs) are epidermal dendritic cells with incompletely understood origins that associate with hair follicles for unknown reasons. Here we show that in response to external stress, mouse hair follicles recruited Gr-1(hi) monocyte-derived precursors of LCs whose epidermal entry was dependent on the chemokine receptors CCR2 and CCR6, whereas the chemokine receptor CCR8 inhibited the recruitment of LCs. Distinct hair-follicle regions had differences in their expression of ligands for CCR2 and CCR6. The isthmus expressed the chemokine CCL2; the infundibulum expressed the chemokine CCL20; and keratinocytes in the bulge produced the chemokine CCL8, which is the ligand for CCR8. Thus, distinct hair-follicle keratinocyte subpopulations promoted or inhibited repopulation with LCs via differences in chemokine production, a feature also noted in humans. Pre-LCs failed to enter hairless skin in mice or humans, which establishes hair follicles as portals for LCs.
引用
收藏
页码:744 / +
页数:11
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