An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy

J. S. Do, A. Visperas, Y. O. Sanogo, J. J. Bechtel, N. Dvorina, S. Kim, E. Jang, S. A. Stohlman, B. Shen, R. L. Fairchild, W. M. Baldwin, D. A A Vignali, B. Min

Research output: Contribution to journalArticle

Abstract

Foxp3-expressing regulatory T cells (Tregs) are central regulators of immune homeostasis and tolerance. As it has been suggested that proper Treg function is compromised under inflammatory conditions, seeking for a pathway that enhances or stabilizes Treg function is a subject of considerable interest. We report that interleukin (IL)-27, an IL-12 family cytokine known to have both pro- and anti-inflammatory roles in T cells, plays a pivotal role in enhancing Treg function to control T cell-induced colitis, a model for inflammatory bowel disease (IBD) in humans. Unlike wild-type (WT) Tregs capable of inhibiting colitogenic T-cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T-cell responses. Tregs stimulated with IL-27 expressed substantially improved suppressive function in vitro and in vivo. IL-27 stimulation of Tregs induced expression of Lag3, a surface molecule implicated in negatively regulating immune responses. Lag3 expression in Tregs was critical to mediate Treg function in suppressing colitogenic responses. Human Tregs also displayed enhanced suppressive function and Lag3 expression following IL-27 stimulation. Collectively, these results highlight a novel function for the IL-27/Lag3 axis in modulating Treg regulation of inflammatory responses in the intestine.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalMucosal Immunology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Interleukin-27
Regulatory T-Lymphocytes
T-Lymphocytes
Cytokines
Therapeutics
Immune Tolerance
Interleukins
Colitis
Interleukin-12
Inflammatory Bowel Diseases
Intestines
Homeostasis
Anti-Inflammatory Agents
Down-Regulation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Do, J. S., Visperas, A., Sanogo, Y. O., Bechtel, J. J., Dvorina, N., Kim, S., ... Min, B. (2016). An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy. Mucosal Immunology, 9(1), 137-145. https://doi.org/10.1038/mi.2015.45

An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy. / Do, J. S.; Visperas, A.; Sanogo, Y. O.; Bechtel, J. J.; Dvorina, N.; Kim, S.; Jang, E.; Stohlman, S. A.; Shen, B.; Fairchild, R. L.; Baldwin, W. M.; Vignali, D. A A; Min, B.

In: Mucosal Immunology, Vol. 9, No. 1, 01.01.2016, p. 137-145.

Research output: Contribution to journalArticle

Do, JS, Visperas, A, Sanogo, YO, Bechtel, JJ, Dvorina, N, Kim, S, Jang, E, Stohlman, SA, Shen, B, Fairchild, RL, Baldwin, WM, Vignali, DAA & Min, B 2016, 'An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy', Mucosal Immunology, vol. 9, no. 1, pp. 137-145. https://doi.org/10.1038/mi.2015.45
Do, J. S. ; Visperas, A. ; Sanogo, Y. O. ; Bechtel, J. J. ; Dvorina, N. ; Kim, S. ; Jang, E. ; Stohlman, S. A. ; Shen, B. ; Fairchild, R. L. ; Baldwin, W. M. ; Vignali, D. A A ; Min, B. / An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy. In: Mucosal Immunology. 2016 ; Vol. 9, No. 1. pp. 137-145.
@article{2cb7b2e01c5a4c198b97c9db71808531,
title = "An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy",
abstract = "Foxp3-expressing regulatory T cells (Tregs) are central regulators of immune homeostasis and tolerance. As it has been suggested that proper Treg function is compromised under inflammatory conditions, seeking for a pathway that enhances or stabilizes Treg function is a subject of considerable interest. We report that interleukin (IL)-27, an IL-12 family cytokine known to have both pro- and anti-inflammatory roles in T cells, plays a pivotal role in enhancing Treg function to control T cell-induced colitis, a model for inflammatory bowel disease (IBD) in humans. Unlike wild-type (WT) Tregs capable of inhibiting colitogenic T-cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T-cell responses. Tregs stimulated with IL-27 expressed substantially improved suppressive function in vitro and in vivo. IL-27 stimulation of Tregs induced expression of Lag3, a surface molecule implicated in negatively regulating immune responses. Lag3 expression in Tregs was critical to mediate Treg function in suppressing colitogenic responses. Human Tregs also displayed enhanced suppressive function and Lag3 expression following IL-27 stimulation. Collectively, these results highlight a novel function for the IL-27/Lag3 axis in modulating Treg regulation of inflammatory responses in the intestine.",
author = "Do, {J. S.} and A. Visperas and Sanogo, {Y. O.} and Bechtel, {J. J.} and N. Dvorina and S. Kim and E. Jang and Stohlman, {S. A.} and B. Shen and Fairchild, {R. L.} and Baldwin, {W. M.} and Vignali, {D. A A} and B. Min",
year = "2016",
month = "1",
day = "1",
doi = "10.1038/mi.2015.45",
language = "English (US)",
volume = "9",
pages = "137--145",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy

AU - Do, J. S.

AU - Visperas, A.

AU - Sanogo, Y. O.

AU - Bechtel, J. J.

AU - Dvorina, N.

AU - Kim, S.

AU - Jang, E.

AU - Stohlman, S. A.

AU - Shen, B.

AU - Fairchild, R. L.

AU - Baldwin, W. M.

AU - Vignali, D. A A

AU - Min, B.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Foxp3-expressing regulatory T cells (Tregs) are central regulators of immune homeostasis and tolerance. As it has been suggested that proper Treg function is compromised under inflammatory conditions, seeking for a pathway that enhances or stabilizes Treg function is a subject of considerable interest. We report that interleukin (IL)-27, an IL-12 family cytokine known to have both pro- and anti-inflammatory roles in T cells, plays a pivotal role in enhancing Treg function to control T cell-induced colitis, a model for inflammatory bowel disease (IBD) in humans. Unlike wild-type (WT) Tregs capable of inhibiting colitogenic T-cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T-cell responses. Tregs stimulated with IL-27 expressed substantially improved suppressive function in vitro and in vivo. IL-27 stimulation of Tregs induced expression of Lag3, a surface molecule implicated in negatively regulating immune responses. Lag3 expression in Tregs was critical to mediate Treg function in suppressing colitogenic responses. Human Tregs also displayed enhanced suppressive function and Lag3 expression following IL-27 stimulation. Collectively, these results highlight a novel function for the IL-27/Lag3 axis in modulating Treg regulation of inflammatory responses in the intestine.

AB - Foxp3-expressing regulatory T cells (Tregs) are central regulators of immune homeostasis and tolerance. As it has been suggested that proper Treg function is compromised under inflammatory conditions, seeking for a pathway that enhances or stabilizes Treg function is a subject of considerable interest. We report that interleukin (IL)-27, an IL-12 family cytokine known to have both pro- and anti-inflammatory roles in T cells, plays a pivotal role in enhancing Treg function to control T cell-induced colitis, a model for inflammatory bowel disease (IBD) in humans. Unlike wild-type (WT) Tregs capable of inhibiting colitogenic T-cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T-cell responses. Tregs stimulated with IL-27 expressed substantially improved suppressive function in vitro and in vivo. IL-27 stimulation of Tregs induced expression of Lag3, a surface molecule implicated in negatively regulating immune responses. Lag3 expression in Tregs was critical to mediate Treg function in suppressing colitogenic responses. Human Tregs also displayed enhanced suppressive function and Lag3 expression following IL-27 stimulation. Collectively, these results highlight a novel function for the IL-27/Lag3 axis in modulating Treg regulation of inflammatory responses in the intestine.

UR - http://www.scopus.com/inward/record.url?scp=84953217393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953217393&partnerID=8YFLogxK

U2 - 10.1038/mi.2015.45

DO - 10.1038/mi.2015.45

M3 - Article

VL - 9

SP - 137

EP - 145

JO - Mucosal Immunology

JF - Mucosal Immunology

SN - 1933-0219

IS - 1

ER -