Project description:We found miR-125a was a key regulator that stabilizes the commitment and immunoregulatory capacity of Treg cells.To gain insights into the general functional features of miR-125a-deficient Treg cells, we performed a genome-wide gene array analysis on Treg population isolated from the spleens of 6 to 8-week-old miR-125a-deficient and WT mice We sorted CD4+CD25hi Treg population from the spleens of 6 to 8-week-old miR-125a-deficient and their littermate WT mice. Cells were collected and total RNA was extracted for Affymetrix GeneChip®Mouse Genome 430 2.0 Array
Project description:Single-cell RNA sequencing (scRNA-seq) was utilized to unbiasedly dissect the cellular heterogeneity of wt vs. Rbx1-deficient CD4+YFP+ Treg cells from the peripheral lymph nodes of inflammation-free female Foxp3cre/wt and Foxp3cre/wt;Rbx1fl/fl mice.
Project description:We found miR-125a was a key regulator that stabilizes the commitment and immunoregulatory capacity of Treg cells.To gain insights into the general functional features of miR-125a-deficient Treg cells, we performed a genome-wide gene array analysis on Treg population isolated from the spleens of 6 to 8-week-old miR-125a-deficient and WT mice
Project description:Cullin-RING Ligases (CRLs), upon activation by neddylation, play the key roles in regulating many biological processes. However, how CRL-neddylation regulates the function of Treg cells remains elusive. Here we show that mice with Treg-specific deletion of Rbx1, a RING component of CRLs required for its activity, developed an early-onset fetal inflammatory disorders and death at day ~25 after birth with disrupted homeostasis and impaired suppressive functions of Treg cells. Specifically, Rbx1 is essential for maintenance of the effector subpopulations in Treg cells, and regulates several inflammatory pathways. Similar phenotypes were seen in mice with deletion of Ube2m, a neddylation E2, in Treg cells, but with much lesser severity. Interestingly, Treg-specific deletion of Rbx2/Sag or Ube2f, the family member of Rbx1 or Ube2m, respectively, had no obvious phenotype. Thus, the Ube2m-Rbx1 axis is required for the maintenance of homeostasis and functions of Treg cells; and Rbx1 has Ube2m-independent roles in the fitness of Treg cells, suggesting a layer of complexity in neddylation activation of CRLs. We use the tranpritome dara to show the mechanism of the function of Rbx1 and Ube2m in Treg cells, also research the relationship of Rbx1 and Ube2m in Treg cells.
Project description:We performed single cell transcriptome analysis of Treg cells (CD4+CD25+) from healthy Mycfl/flFoxp3Cre/WT female mice, in which Myc-sufficient (WT) and Myc-deficient (KO) Treg cells co-exist due to random inactivation of the X chromosome that harbors the Foxp3 gene.
Project description:LKB1 deficiency in Treg cells impairs their survival, metabolism and suppressive function. To exclude the impact of excessive inflammation on LKB1-deficient Treg cells, we generated mixed bone marrow (BM) chimeras using Foxp3-Cre WT and Foxp3-Cre Stk11 fl/fl BM cells, together with CD45.1+ BM cells. We used microarray to compare the global transcription profile of dornor-derived LKB1-deficient Tregs with WT counterparts.
Project description:The importance of regulatory T cells (Treg) for immune tolerance is well recognized, yet the signaling molecules influencing their suppressive activity are relatively poorly understood. We identified the cytoplasmic tyrosine phosphatase SHP-1 as a novel ‘endogenous brake’ and modifier of the suppressive ability of Treg cells; consistent with this notion, loss of SHP-1 expression strongly augments the ability of Treg cells to suppress inflammation in a mouse model. Specific harmacological inhibition of SHP-1 enzymatic activity via the cancer drug sodium stibogluconate (SSG) potently augmented Treg cell suppressor activity both in vivo and ex vivo. We evaluated the gene expression profiles of sorted T reg cells (CD4+CD25+) from wild type (wt) mice and mice that were heterozygous (he) or homozygous (me) for SHP-1 knockout (motheaten phenotype). T reg (CD4+CD25+) cells were isolated form wild type (WT) mice and that were heterozygous (he) or homozygous (me) for SHP-1 knockout (motheaten phenotype); totalRNA was isolated using Arcturus reagents; aRNA was generated and amplified using Arcturus reagents; and labeled product was hybridized to Affymetrix chips to asses gene expression patterns.