Foxp3+ regulatory T (Treg) cells prevent inflammatory disease but the mechanistic basis of suppression is not understood completely . Gene silencing by RNA interference can act in a cell-autonomous and non-cell-autonomous manner, providing mechanisms of inter-cellular regulation. Here, we demonstrate that non-cell-autonomous gene silencing, mediated by miRNA-containing exosomes, is a mechanism employed by Treg cells to suppress T cell-mediated disease. Treg cells transferred microRNAs (miRNA) to various immune cells, including T helper 1 (Th1) cells, suppressing Th1 cell proliferation and cytokine secretion. Use of Dicer-deficient or Rab27a and Rab27b double-deficient Treg cells to disrupt miRNA-biogenesis or the exosomal pathway, respectively, established a requirement for miRNAs and exosomes for Treg cell-mediated suppression. Transcriptional analysis and miRNA inhibitor studies showed that exosome-mediated transfer of Let-7d from Treg cell to Th1 cells contributed to suppression and prevention of systemic disease. These studies reveal a mechanism of Treg cell-mediated suppression mediated by miRNA-containing exosomes.
MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells.
Specimen part
View SamplesGene expression of Treg cells that have lost Foxp3 expression and acquired Il4 expression following adoptive transfer into T-cell deficient mice (HpTR-IL-4gfp+), cmpared to conventional Treg cells isolated from H. polygyrus-infected wild-type mice (HpTR) and Th2 cells generated from nave T cells following adoptive transfer into H. polygyrus-infected T-cell deficient mice (nT-IL-4gfp+).
Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
H2.0-like homeobox regulates early hematopoiesis and promotes acute myeloid leukemia.
Specimen part, Cell line
View SamplesThe goal was to study the role of Hlx in hematopoiesis.
H2.0-like homeobox regulates early hematopoiesis and promotes acute myeloid leukemia.
Specimen part
View SamplesTo study the role of Hlx in hematopoietic differentiation and tumorigenesis, URE cells were infected with short-hairpin-containing pSIH1-H1-copGFP lentiviral vector (System Biosciences, Mountain View, CA) containing either nucleotide sequences targeting luciferase (shControl) or HLX (shHLX). After 24hrs incubation in Iscoves modified Dulbeccos medium (IMDM) containing FBS, mIL-3, mIL-6 and mSCF with lentiviral supernatants in the presence of 8ug/ml polybrene, cells were cultured in fresh medium for several days. Subsequently, GFP+ cells were sorted by FACS and RNA was prepared.
H2.0-like homeobox regulates early hematopoiesis and promotes acute myeloid leukemia.
Cell line
View SamplesGene expression analysis on purified murine hematopoietic stem cells (HSCs) deficient for Special AT-rich sequence-binding protein 1 (Satb1) compared to wild-type HSCs.
Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers.
Specimen part, Cell line, Treatment
View SamplesHodgkin lymphoma is derived from germinal center / post-germinal center B cells.
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers.
Specimen part, Cell line
View SamplesDescription of differentially expressed genes between KMH2 CIITA-BX648577 knockdown cultures and non-silencing controls
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
New IDH1 mutant inhibitors for treatment of acute myeloid leukemia.
Specimen part
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