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Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
- Source :
-
Immunity [Immunity] 2015 Mar 17; Vol. 42 (3), pp. 499-511. Date of Electronic Publication: 2015 Mar 10. - Publication Year :
- 2015
-
Abstract
- CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARĪ±, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARĪ± as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells.<br /> (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Differentiation drug effects
Cell Differentiation immunology
Cell Lineage immunology
Gene Expression Regulation
Gene Regulatory Networks
Homeostasis drug effects
Homeostasis immunology
Integrases genetics
Integrases metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Retinoic Acid immunology
Retinoic Acid Receptor alpha
Signal Transduction
T-Lymphocytes, Helper-Inducer cytology
T-Lymphocytes, Helper-Inducer immunology
Th1 Cells cytology
Th1 Cells immunology
Th17 Cells cytology
Th17 Cells immunology
Tretinoin immunology
Cell Lineage drug effects
Receptors, Retinoic Acid genetics
T-Lymphocytes, Helper-Inducer drug effects
Th1 Cells drug effects
Th17 Cells drug effects
Tretinoin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 42
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 25769610
- Full Text :
- https://doi.org/10.1016/j.immuni.2015.02.003