Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein

Li Fan Lu; To Ha Thai; Dinis Pedro Calado; Ashutosh Chaudhry; Masato Kubo; Kentaro Tanaka; Gabriel B. Loeb; Hana Lee; Akihiko Yoshimura; Klaus Rajewsky; Alexander Y. Rudensky

doi:10.1016/j.immuni.2008.11.010

Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein

Li Fan Lu, To Ha Thai, Dinis Pedro Calado, Ashutosh Chaudhry, Masato Kubo, Kentaro Tanaka, Gabriel B. Loeb, Hana Lee, Akihiko Yoshimura, Klaus Rajewsky, Alexander Y. Rudensky

Department of Respirology

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

676 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	80-91
Number of pages	12
Journal	Immunity
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2008.11.010
Publication status	Published - Jan 16 2009

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2008.11.010

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@article{0946032ad32f493da0b9f62e0cdb3a67,

title = "Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein",

abstract = "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.",

author = "Lu, {Li Fan} and Thai, {To Ha} and Calado, {Dinis Pedro} and Ashutosh Chaudhry and Masato Kubo and Kentaro Tanaka and Loeb, {Gabriel B.} and Hana Lee and Akihiko Yoshimura and Klaus Rajewsky and Rudensky, {Alexander Y.}",

note = "Funding Information: We thank S. Josefowicz for the help in key experiments, T. Chu, L. Karpik, and K. Forbush for superb technical assistance, and all members of our laboratory for discussions. This work was supported by grants from the National Institutes of Health (to A.Y.R. and K.R.), from the European Union through MUGEN (to K.R.), and from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (to A.Y.). L.L.F. is a Leukemia and Lymphoma Society Fellow. D.P.C. is supported by the Portuguese Foundation for Science and Technology (FCR-MCES). A.Y.R. is a Howard Hughes Medical Institute investigator. ",

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doi = "10.1016/j.immuni.2008.11.010",

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T1 - Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein

AU - Lu, Li Fan

AU - Thai, To Ha

AU - Calado, Dinis Pedro

AU - Chaudhry, Ashutosh

AU - Kubo, Masato

AU - Tanaka, Kentaro

AU - Loeb, Gabriel B.

AU - Lee, Hana

AU - Yoshimura, Akihiko

AU - Rajewsky, Klaus

AU - Rudensky, Alexander Y.

N1 - Funding Information: We thank S. Josefowicz for the help in key experiments, T. Chu, L. Karpik, and K. Forbush for superb technical assistance, and all members of our laboratory for discussions. This work was supported by grants from the National Institutes of Health (to A.Y.R. and K.R.), from the European Union through MUGEN (to K.R.), and from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (to A.Y.). L.L.F. is a Leukemia and Lymphoma Society Fellow. D.P.C. is supported by the Portuguese Foundation for Science and Technology (FCR-MCES). A.Y.R. is a Howard Hughes Medical Institute investigator.

PY - 2009/1/16

Y1 - 2009/1/16

N2 - 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.

AB - 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.

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Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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