Genomics

Dataset Information

38

Excessive miR-27 expression impairs regulatory T cell-mediated immunological tolerance [CD4cre miR-23 clusterTg Tr]


ABSTRACT: MicroRNAs (miRNAs) are tightly regulated in the immune system, as aberrant expression of miRNAs often results in hematopoietic malignancies and autoimmune diseases. Previously, elevated levels of miR-27 in T cells isolated from multiple sclerosis patients has been suggested to facilitate disease progression through inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we demonstrate that while mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology, these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous manner but rather resulted from a perturbed regulatory T (Treg) cell compartment. Excessive miR-27 expression in T cells severely impairs Treg cell differentiation. Moreover, Treg cells with exaggerated miR-27-mediated gene regulation exhibit diminished homeostasis and suppressor function in vivo. Mechanistically, miR-27 represses several known as well as previously uncharacterized targets that play critical roles in controlling multiple aspects of Treg cell biology. Collectively, our data show miR-27 functions as a key regulator in Treg cell development and function and suggest that proper regulation of miR-27 is pivotal to safeguard Treg cell-mediated immunological tolerance. Overall design: Treg cells isolated from mice with T cell-specific overexpression of the entire miR-23 cluster or individual miR-23 family members as well as from mice with T cell-specific deletion of both miR-23a/b clusters.

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

ORGANISM(S): Mus Musculus

SUBMITTER: Li-Fan Lu  

PROVIDER: GSE89546 | GEO | 2016-11-05

SECONDARY ACCESSION(S): PRJNA352587

REPOSITORIES: GEO

Dataset's files

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GSE89546_CD4cre_miR-23_clusterTg_Tr_RPKM.txt.gz Txt
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Publications

Excessive expression of miR-27 impairs Treg-mediated immunological tolerance.

Cruz Leilani O LO   Hashemifar Somaye Sadat SS   Wu Cheng-Jang CJ   Cho Sunglim S   Nguyen Duc T DT   Lin Ling-Li LL   Khan Aly Azeem AA   Lu Li-Fan LF  

The Journal of clinical investigation 20170109 2


MicroRNAs (miRs) are tightly regulated in the immune system, and aberrant expression of miRs often results in hematopoietic malignancies and autoimmune diseases. Previously, it was suggested that elevated levels of miR-27 in T cells isolated from patients with multiple sclerosis facilitate disease progression by inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we have demonstrated that, although mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 respon  ...[more]

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