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Status |
Public on Oct 08, 2019 |
Title |
Calcitonin gene related peptide negatively regulates alarmin-driven type 2 innate lymphoid cell responses |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Neuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed both the neuropeptide CGRP (Calcitonin Gene-Related Peptide) and its receptor. CGRP potently inhibited alarmin-driven type 2 cytokine production and proliferation by lung ILC2s both in vitro and in vivo. CGRP induced marked changes in ILC2 expression programs in vivo and in vitro, attenuating alarmin-driven proliferative and effector responses. A distinct subset of ILCs scored highly for a CGRP-specific gene signature after in vivo alarmin stimulation, suggesting CGRP regulated this response. Finally, we observed increased ILC2 proliferation and type 2 cytokine production and exaggerated responses to alarmins in mice lacking the CGRP receptor. Together, these data indicate that endogenous CGRP is a critical negative regulator of ILC2 responses in vivo.
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Overall design |
For in vitro bulk RNA-seq experiments, there are 32 samples total, representing 2 biological replicates, each split into 2 technical replicates, of 4 conditions at 2 time points. For in vivo scRNA-seq experiments, there are 8 samples total, representing 2 biological replicates of 4 conditions at 1 time point. For in vitro ATAC-seq experiments, there are 6 samples total, representing 3 replicates of 2 conditions at 1 time point.
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Contributor(s) |
Wallrapp A, Burkett PR, Riesenfeld SJ, Kim S, Christian E, Abdulnour RE, Thakore PI, Schnell A, Lambden C, Herbst R, Khan P, Tsujikawa K, Chiu IM, Levy BD, Regev A, Kuchroo VK |
Citation missing |
Has this study been published? Please login to update or notify GEO. |
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Submission date |
Aug 21, 2019 |
Last update date |
Oct 08, 2019 |
Contact name |
Samantha Riesenfeld |
Organization name |
Broad Institute
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Lab |
Regev
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Street address |
415 Main St
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City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02142 |
Country |
USA |
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Platforms (3) |
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Samples (46)
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Relations |
BioProject |
PRJNA561400 |
SRA |
SRP219030 |
Supplementary file |
Size |
Download |
File type/resource |
GSE136154_ATAC_all.normalized_counts.txt.gz |
3.1 Mb |
(ftp)(http) |
TXT |
GSE136154_ATAC_all.rawcounts.tab.gz |
1.5 Mb |
(ftp)(http) |
TAB |
GSE136154_Bulk_all.matrix.abundance_TPM.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
GSE136154_Bulk_all.matrix.counts.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
GSE136154_CGRP_1.filtered_feature_bc_matrix.h5 |
11.3 Mb |
(ftp)(http) |
H5 |
GSE136154_CGRP_2.filtered_feature_bc_matrix.h5 |
12.7 Mb |
(ftp)(http) |
H5 |
GSE136154_IL33_1.filtered_feature_bc_matrix.h5 |
16.3 Mb |
(ftp)(http) |
H5 |
GSE136154_IL33_2.filtered_feature_bc_matrix.h5 |
17.3 Mb |
(ftp)(http) |
H5 |
GSE136154_IL33_CGRP_1.filtered_feature_bc_matrix.h5 |
13.1 Mb |
(ftp)(http) |
H5 |
GSE136154_IL33_CGRP_2.filtered_feature_bc_matrix.h5 |
14.3 Mb |
(ftp)(http) |
H5 |
GSE136154_PBS_1.filtered_feature_bc_matrix.h5 |
12.3 Mb |
(ftp)(http) |
H5 |
GSE136154_PBS_2.filtered_feature_bc_matrix.h5 |
10.9 Mb |
(ftp)(http) |
H5 |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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