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Series GSE211511 Query DataSets for GSE211511
Status Public on Aug 24, 2022
Title MARCH1 controls an exhaustion-like program of effector CD4+ T cells promoting allergic airway inflammation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Persistent antigenic signalling leads to T cell exhaustion, a dysfunctional state arising in many chronic infections and cancers. Little is known concerning mechanisms limiting exhaustion in immune stimulatory diseases such as asthma. We report that membrane-associated RING-CH1 (MARCH1), the ubiquitin ligase that mediates surface turnover of MHCII and CD86 in professional APCs, plays an essential role in restraining exhaustion of effector CD4+ T cells in a mouse model of asthma. Mice lacking MARCH1 or the ubiquitin acceptor sites of MHCII and CD86 exhibited increased MHCII and CD86 surface expression on lung APCs, and this increase promoted enhanced expression of immune inhibitory receptors by effector CD4+ T cells and inhibited their proliferation. Remarkably, ablation of MARCH1 in mice with established asthma reduced airway infiltration of eosinophils and Th2 cells. Thus, MARCH1 controls exhaustion of effector CD4+ T cells during allergic airway inflammation and may serve as a therapeutic target for asthma.
Overall design WT mice were sensitized to house dust mite (HDM) by repeated oropharyngeal aspiration of HDM extract (days 0, 7-11). On day 14, donor CD4 T cells were enriched from the lung, labeled with Cell Trace Violet (CTV) and adoptively transferred into WT or KO mice. Recipient mice were then challenged with HDM extract and at day 4 post challenge, CTV low (proliferating) donor cells were sorted from the lung for scRNA-seq.
Contributor(s) Castellanos CA, Hiam-Galvez KJ, Ishido S, Satpathy AT, Shin J
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Submission date Aug 17, 2022
Last update date Aug 31, 2022
Contact name Kamir Hiam-Galvez
Organization name Stanford University
Street address 240 Pasteur Drive
City Stanford
ZIP/Postal code 94304
Country USA
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (2)
GSM6474925 WT
GSM6474926 KO
BioProject PRJNA870581

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Supplementary file Size Download File type/resource
GSE211511_RAW.tar 12.5 Mb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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