Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein.
Foxp3(+) regulatory T (Treg) cells limit pathogenic immune responses to self-antigens and foreign antigens. An essential role for microRNA (miRNA) in the maintenance and function of Treg cells, revealed by the Treg cell-specific Dicer ablation, raised a question as to a specific miRNA contribution. We found that Foxp3 controlled the elevated miR155 expression required for maintaining Treg cell proliferative activity and numbers under nonlymphopenic conditions. Moreover, miR155 deficiency in Treg cells resulted in increased suppressor of cytokine signaling 1 (SOCS1) expression accompanied by impaired activation of signal transducer and activator of transcription 5 (STAT5) transcription factor in response to limiting amounts of interleukin-2. Our studies suggest that Foxp3-dependent regulation of miR155 maintains competitive fitness of Treg cell subsets by targeting SOCS1, and they provide experimental support for a proposed role for miRNAs in ensuring the robustness of cellular phenotypes.
Lu
Li-Fan
LF
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Thai
To-Ha
TH
Calado
Dinis Pedro
DP
Chaudhry
Ashutosh
A
Kubo
Masato
M
Tanaka
Kentaro
K
Loeb
Gabriel B
GB
Lee
Hana
H
Yoshimura
Akihiko
A
Rajewsky
Klaus
K
Rudensky
Alexander Y
AY
D000818:Animals; D001483:Base Sequence; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D035683:MicroRNAs; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins