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| 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
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| 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.
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| 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.
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| Contributor(s) |
Castellanos CA, Hiam-Galvez KJ, Ishido S, Satpathy AT, Shin J |
| Citation missing |
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| Submission date |
Aug 17, 2022 |
| Last update date |
Aug 31, 2022 |
| Contact name |
Kamir Hiam-Galvez |
| E-mail(s) |
khiamg@stanford.edu
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| Organization name |
Stanford University
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| Street address |
240 Pasteur Drive
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| City |
Stanford |
| ZIP/Postal code |
94304 |
| Country |
USA |
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| Platforms (1) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA870581 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE211511_RAW.tar |
12.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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