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

Autor: Jennifer J. Bechtel, Nina Dvorina, Stephen A. Stohlman, Dario A. A. Vignali, Bo Shen, Booki Min, Robert L. Fairchild, William M. Baldwin, Eun Jung Jang, Yibayiri O. Sanogo, Jeong-su Do, Anabelle Visperas, Sohee Kim
Rok vydání: 2015
Předmět:
0301 basic medicine
Interleukin-27
LAG3
Regulatory T cell
colitis
medicine.medical_treatment
Immunology
Primary Cell Culture
IBD
chemical and pharmacologic phenomena
Biology
Lymphocyte Activation
T-Lymphocytes
Regulatory
Article
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
Antigens
CD
medicine
Immunology and Allergy
Animals
Humans
Lymphocyte activation gene 3
Cell Proliferation
Regulation of gene expression
Mice
Knockout
Interleukins
Interleukin
FOXP3
hemic and immune systems
Forkhead Transcription Factors
Receptors
Interleukin
Lymphocyte Activation Gene 3 Protein
CD4
3. Good health
Mice
Inbred C57BL
Treg
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Cytokine
Gene Expression Regulation
Signal transduction
030215 immunology
Signal Transduction
Zdroj: Mucosal immunology
ISSN: 1935-3456
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: