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
相关论文
共 55 条
[21]
Cutting Edge: Memory Regulatory T Cells Require IL-7 and Not IL-2 for Their Maintenance in Peripheral Tissues [J].
Gratz, Iris K. ;
Truong, Hong-An ;
Yang, Sara Hsin-Yi ;
Maurano, Megan M. ;
Lee, Karim ;
Abbas, Abul K. ;
Rosenblum, Michael D. .
JOURNAL OF IMMUNOLOGY, 2013, 190 (09) :4483-4487
[22]
Visualization of immediate immune responses to pioneer metastatic cells in the lung [J].
Headley, Mark B. ;
Bins, Adriaan ;
Nip, Alyssa ;
Roberts, Edward W. ;
Looney, Mark R. ;
Gerard, Audrey ;
Krummel, Matthew F. .
NATURE, 2016, 531 (7595) :513-+
[23]
Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis [J].
Ito, M ;
Liu, YP ;
Yang, ZX ;
Nguyen, J ;
Liang, F ;
Morris, RJ ;
Cotsarelis, G .
NATURE MEDICINE, 2005, 11 (12) :1351-1354
[24]
Lgr5 marks cycling, yet long-lived, hair follicle stem cells [J].
Jaks, Viljar ;
Barker, Nick ;
Kasper, Maria ;
Van Es, Johan H. ;
Snippert, Hugo J. ;
Clevers, Hans ;
Toftgard, Rune .
NATURE GENETICS, 2008, 40 (11) :1291-1299
[25]
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice [J].
Kim, Jeong M. ;
Rasmussen, Jeffrey P. ;
Rudensky, Alexander Y. .
NATURE IMMUNOLOGY, 2007, 8 (02) :191-197
[26]
Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis [J].
Lecuit, Thomas ;
Lenne, Pierre-Francois .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (08) :633-644
[27]
Distinct stem cell populations regenerate the follicle and interfollicular epidermis [J].
Levy, V ;
Lindon, C ;
Harfe, BD ;
Morgan, BA .
DEVELOPMENTAL CELL, 2005, 9 (06) :855-861
[28]
Li H, 2009, BIOINFORMATICS, V25, P1094, DOI [10.1093/bioinformatics/btp100, 10.1093/bioinformatics/btp324]
[29]
Regulatory T cell development in the absence of functional Foxp3 [J].
Lin, Wen ;
Haribhai, Dipica ;
Relland, Lance M. ;
Truong, Nga ;
Carlson, Marc R. ;
Williams, Calvin B. ;
Chatila, Talal A. .
NATURE IMMUNOLOGY, 2007, 8 (04) :359-368
[30]
Antigen Recognition in the Islets Changes with Progression of Autoimmune Islet Infiltration [J].
Lindsay, Robin S. ;
Corbin, Kaitlin ;
Mahne, Ashley ;
Levitt, Bonnie E. ;
Gebert, Matthew J. ;
Wigton, Eric J. ;
Bradley, Brenda J. ;
Haskins, Kathryn ;
Jacobelli, Jordan ;
Tang, Qizhi ;
Krummel, Matthew F. ;
Friedman, Rachel S. .
JOURNAL OF IMMUNOLOGY, 2015, 194 (02) :522-530