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| Status |
Public on Jan 31, 2022 |
| Title |
IL-9 is required for multi-cytokine producing tissue-resident memory CD4+ T cell-dependent allergic airway recall responses |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Asthma is a chronic inflammatory lung disease with intermittent flares predominately mediated through memory T cells. Yet, the identity of long-term memory cells that mediate allergic recall responses are not well defined. In this report, using a mouse model of chronic allergen exposure followed by an allergen-free rest period, we have characterized a sub-population of Th2 cells that secretes IL-9 as an obligate effector cytokine. IL-9-secreting cells have a resident memory T cell phenotype and blocking IL-9 during a recall challenge significantly diminishes airway inflammation and airway hyperreactivity. T cells secrete IL-9 in response to allergen recall and secretion is amplified by IL-33. Using scRNA-seq and scATAC-seq, we define the cellular identity of a distinct populations of T cells with pro-allergic cytokine patterns. Thus, in a recall model of allergic airway inflammation, IL-9 secretion from a multi-cytokine producing cell population is required for an allergen recall response.
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| Overall design |
1. To compare transcriptional profile of ST2+CD4 T cells and ST2- CD4 T cells in the lung, ST2+ and ST2- CD4 T cells were isolated from the lung in a recall model and pooled together to generate replicates of ST2+ CD4 T cells and ST2- CD4 T cells, with a total of 4 samples for scRNA-seq and snATAC-seq analysis. 2. To examine to the function of IL-9 in allergic recall response, single suspension of total viable cells from the lung were generated from the mice that were treated with anti-IL-9 or isotype (100 μg/ml) during the recall challenge. For this experiment three replicates of total lung cells after anti-IL-9 or isotype treatment were used for scRNA-seq analysis.
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| Contributor(s) |
Kaplan MH, Ulrich BJ, Kharwadkar R, Gao H |
| Citation(s) |
35302861 |
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| Submission date |
Dec 13, 2021 |
| Last update date |
May 02, 2022 |
| Contact name |
Rakshin Kharwadkar |
| E-mail(s) |
rkharwad@iu.edu
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| Organization name |
Indiana University School of Medicine
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| Department |
Microbiology and Immunology
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| Street address |
635 Branhill Dr., 418 MS building
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| City |
Indianapolis |
| State/province |
Indiana |
| ZIP/Postal code |
46202 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA788490 |
| SRA |
SRP350543 |
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