Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation

Niwa Ali, Bahar Zirak, Robert Sanchez Rodriguez, Mariela L. Pauli, Hong An Truong, Kevin Lai, Richard Ahn, Kaitlin Corbin, Margaret M. Lowe, Tiffany C. Scharschmidt, Keyon Taravati, Madeleine R. Tan, Roberto R. Ricardo-Gonzalez, Audrey Nosbaum, Marta Bertolini, Wilson Liao, Frank O. Nestle, Ralf Paus, George Cotsarelis, Abul K. Abbas & 1 others Michael D. Rosenblum

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1119-1129.e11
JournalCell
Volume169
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Fingerprint

T-cells
Hair Follicle
Regulatory T-Lymphocytes
Stem cells
Cell Differentiation
Skin
Stem Cells
Epithelial Cells
Tissue homeostasis
Tissue
Regeneration
Ligands
Homeostasis
Maintenance

Keywords

  • alopecia areata
  • hair
  • hair follicle stem cell
  • hair regeneration
  • Jagged 1
  • Notch
  • regulatory T cell
  • skin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ali, N., Zirak, B., Rodriguez, R. S., Pauli, M. L., Truong, H. A., Lai, K., ... Rosenblum, M. D. (2017). Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. Cell, 169(6), 1119-1129.e11. https://doi.org/10.1016/j.cell.2017.05.002

Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. / Ali, Niwa; Zirak, Bahar; Rodriguez, Robert Sanchez; Pauli, Mariela L.; Truong, Hong An; Lai, Kevin; Ahn, Richard; Corbin, Kaitlin; Lowe, Margaret M.; Scharschmidt, Tiffany C.; Taravati, Keyon; Tan, Madeleine R.; Ricardo-Gonzalez, Roberto R.; Nosbaum, Audrey; Bertolini, Marta; Liao, Wilson; Nestle, Frank O.; Paus, Ralf; Cotsarelis, George; Abbas, Abul K.; Rosenblum, Michael D.

In: Cell, Vol. 169, No. 6, 01.06.2017, p. 1119-1129.e11.

Research output: Contribution to journalArticle

Ali, N, Zirak, B, Rodriguez, RS, Pauli, ML, Truong, HA, Lai, K, Ahn, R, Corbin, K, Lowe, MM, Scharschmidt, TC, Taravati, K, Tan, MR, Ricardo-Gonzalez, RR, Nosbaum, A, Bertolini, M, Liao, W, Nestle, FO, Paus, R, Cotsarelis, G, Abbas, AK & Rosenblum, MD 2017, 'Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation', Cell, vol. 169, no. 6, pp. 1119-1129.e11. https://doi.org/10.1016/j.cell.2017.05.002
Ali N, Zirak B, Rodriguez RS, Pauli ML, Truong HA, Lai K et al. Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. Cell. 2017 Jun 1;169(6):1119-1129.e11. https://doi.org/10.1016/j.cell.2017.05.002
Ali, Niwa ; Zirak, Bahar ; Rodriguez, Robert Sanchez ; Pauli, Mariela L. ; Truong, Hong An ; Lai, Kevin ; Ahn, Richard ; Corbin, Kaitlin ; Lowe, Margaret M. ; Scharschmidt, Tiffany C. ; Taravati, Keyon ; Tan, Madeleine R. ; Ricardo-Gonzalez, Roberto R. ; Nosbaum, Audrey ; Bertolini, Marta ; Liao, Wilson ; Nestle, Frank O. ; Paus, Ralf ; Cotsarelis, George ; Abbas, Abul K. ; Rosenblum, Michael D. / Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. In: Cell. 2017 ; Vol. 169, No. 6. pp. 1119-1129.e11.
@article{dfaa02132779428f9dc291278be03392,
title = "Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation",
abstract = "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.",
keywords = "alopecia areata, hair, hair follicle stem cell, hair regeneration, Jagged 1, Notch, regulatory T cell, skin",
author = "Niwa Ali and Bahar Zirak and Rodriguez, {Robert Sanchez} and Pauli, {Mariela L.} and Truong, {Hong An} and Kevin Lai and Richard Ahn and Kaitlin Corbin and Lowe, {Margaret M.} and Scharschmidt, {Tiffany C.} and Keyon Taravati and Tan, {Madeleine R.} and Ricardo-Gonzalez, {Roberto R.} and Audrey Nosbaum and Marta Bertolini and Wilson Liao and Nestle, {Frank O.} and Ralf Paus and George Cotsarelis and Abbas, {Abul K.} and Rosenblum, {Michael D.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1016/j.cell.2017.05.002",
language = "English (US)",
volume = "169",
pages = "1119--1129.e11",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation

AU - Ali, Niwa

AU - Zirak, Bahar

AU - Rodriguez, Robert Sanchez

AU - Pauli, Mariela L.

AU - Truong, Hong An

AU - Lai, Kevin

AU - Ahn, Richard

AU - Corbin, Kaitlin

AU - Lowe, Margaret M.

AU - Scharschmidt, Tiffany C.

AU - Taravati, Keyon

AU - Tan, Madeleine R.

AU - Ricardo-Gonzalez, Roberto R.

AU - Nosbaum, Audrey

AU - Bertolini, Marta

AU - Liao, Wilson

AU - Nestle, Frank O.

AU - Paus, Ralf

AU - Cotsarelis, George

AU - Abbas, Abul K.

AU - Rosenblum, Michael D.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

KW - alopecia areata

KW - hair

KW - hair follicle stem cell

KW - hair regeneration

KW - Jagged 1

KW - Notch

KW - regulatory T cell

KW - skin

UR - http://www.scopus.com/inward/record.url?scp=85019884126&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019884126&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.05.002

DO - 10.1016/j.cell.2017.05.002

M3 - Article

VL - 169

SP - 1119-1129.e11

JO - Cell

JF - Cell

SN - 0092-8674

IS - 6

ER -