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; Michael D. Rosenblum

doi:10.1016/j.cell.2017.05.002

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. AbbasMichael D. Rosenblum^*

^*Corresponding author for this work

Division of Musculoskeletal & Dermatological Sciences (L5)

Research output: Contribution to journal › Article › peer-review

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 T_regs 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. Localized regulatory T cells (Tregs) regulate the hair follicle cycle by driving Notch-dependent stem cell proliferation and differentiation.

Original language	English
Journal	Cell
Volume	169
Issue number	6
Early online date	25 May 2017
DOIs	https://doi.org/10.1016/j.cell.2017.05.002
Publication status	Published - 1 Jun 2017

Keywords

Alopecia areata
Hair
Hair follicle stem cell
Hair regeneration
Jagged 1
Notch
Regulatory T cell
Skin

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10.1016/j.cell.2017.05.002

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Ali, N., Zirak, B., Rodriguez, R. S., Pauli, M. L., Truong, H. A., Lai, K., Ahn, R., Corbin, K., Lowe, M. M., Scharschmidt, T. C., Taravati, K., Tan, M. R., Ricardo-Gonzalez, R. R., Nosbaum, A., Bertolini, M., Liao, W., Nestle, F. O., Paus, R., Cotsarelis, G., ... Rosenblum, M. D. (2017). Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. Cell, 169(6). https://doi.org/10.1016/j.cell.2017.05.002

@article{5afc7137724e4ad1b0296c1b9b7e0c1b,

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. Localized regulatory T cells (Tregs) regulate the hair follicle cycle by driving Notch-dependent stem cell proliferation and differentiation.",

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 = jun,

day = "1",

doi = "10.1016/j.cell.2017.05.002",

language = "English",

volume = "169",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier BV",

number = "6",

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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. https://doi.org/10.1016/j.cell.2017.05.002

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. Localized regulatory T cells (Tregs) regulate the hair follicle cycle by driving Notch-dependent stem cell proliferation and differentiation.

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. Localized regulatory T cells (Tregs) regulate the hair follicle cycle by driving Notch-dependent stem cell proliferation and differentiation.

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

U2 - 10.1016/j.cell.2017.05.002

DO - 10.1016/j.cell.2017.05.002

M3 - Article

AN - SCOPUS:85019884126

SN - 0092-8674

VL - 169

JO - Cell

JF - Cell

IS - 6

ER -

Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation

Abstract

Keywords

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