Induced miR‐99a expression represses Mtor cooperatively with miR‐150 to promote regulatory T‐cell differentiation

Autor: Anian Hiekel, K. Mark Ansel, Sebastian C. Warth, Vigo Heissmeyer, Ludger Klein, Karsten Kretschmer, Kai P. Hoefig, Sonja Schallenberg, Ksenija Jovanovic
Rok vydání: 2015
Předmět:
CD4-Positive T-Lymphocytes
Ribonuclease III
Regulatory T cell differentiation
Green Fluorescent Proteins
Molecular Sequence Data
Retinoic acid
Mice
Transgenic
Tretinoin
chemical and pharmacologic phenomena
Endogeny
Biology
T-Lymphocytes
Regulatory
General Biochemistry
Genetics and Molecular Biology
DEAD-box RNA Helicases
Treg Cells
T‐cell Differentiation
Mirna Function
chemistry.chemical_compound
Immune system
miR-150
microRNA
Animals
Gene Regulatory Networks
3' Untranslated Regions
Molecular Biology
Cells
Cultured
PI3K/AKT/mTOR pathway
Base Sequence
General Immunology and Microbiology
TOR Serine-Threonine Kinases
General Neuroscience
Cell Differentiation
hemic and immune systems
Cell biology
Mice
Inbred C57BL
MicroRNAs
Have You Seen?
Gene Expression Regulation
chemistry
T cell differentiation
Immunology
Zdroj: EMBO J. 34, 1195-1213 (2015)
ISSN: 1460-2075
0261-4189
DOI: 10.15252/embj.201489589
Popis: Peripheral induction of regulatory T (Treg) cells provides essential protection from inappropriate immune responses. CD4 + T cells that lack endogenous miRNAs are impaired to differentiate into Treg cells, but the relevant miRNAs are unknown. We performed an overexpression screen with T‐cell‐expressed miRNAs in naive mouse CD4 + T cells undergoing Treg differentiation. Among 130 candidates, the screen identified 29 miRNAs with a negative and 10 miRNAs with a positive effect. Testing reciprocal Th17 differentiation revealed specific functions for miR‐100, miR‐99a and miR‐10b, since all of these promoted the Treg and inhibited the Th17 program without impacting on viability, proliferation and activation. miR‐99a cooperated with miR‐150 to repress the expression of the Th17‐promoting factor mTOR. The comparably low expression of miR‐99a was strongly increased by the Treg cell inducer “retinoic acid”, and the abundantly expressed miR‐150 could only repress Mtor in the presence of miR‐99a. Our data suggest that induction of Treg cell differentiation is regulated by a miRNA network, which involves cooperation of constitutively expressed as well as inducible miRNAs.
Databáze: OpenAIRE
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