Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation

被引:544
作者
Ali, Niwa [1 ,3 ]
Zirak, Bahar [1 ]
Rodriguez, Robert Sanchez [1 ]
Pauli, Mariela L. [1 ]
Hong-An Truong [1 ]
Lai, Kevin [1 ]
Ahn, Richard [1 ]
Corbin, Kaitlin [2 ]
Lowe, Margaret M. [1 ]
Scharschmidt, Tiffany C. [1 ]
Taravati, Keyon [1 ]
Tan, Madeleine R. [1 ]
Ricardo-Gonzalez, Roberto R. [1 ]
Nosbaum, Audrey [1 ]
Bertolini, Marta [4 ]
Liao, Wilson [1 ]
Nestle, Frank O. [3 ]
Paus, Ralf [5 ,6 ]
Cotsarelis, George [7 ]
Abbas, Abul K. [2 ]
Rosenblum, Michael D. [1 ]
机构
[1] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
[3] Kings Coll London, St Johns Inst Dermatol, Cutaneous Med Unit, London WC2R 2LS, England
[4] Univ Munster, Dept Dermatol, D-48149 Munster, Germany
[5] Univ Manchester, Ctr Dermatol Res, Manchester M13 9PL, Lancs, England
[6] NIHR Manchester Biomed Res Ctr, Manchester M13 9PL, Lancs, England
[7] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA
关键词
HAIR FOLLICLE BULGE; DENDRITIC CELLS; SELF-RENEWAL; IN-VITRO; HOMEOSTASIS; POPULATION; RESIDENT; JAGGED-1; INHIBIT; INNATE;
D O I
10.1016/j.cell.2017.05.002
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
The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.
引用
收藏
页码:1119 / +
页数:22
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