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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 12, 2024 |
| Title |
Single-cell RNAseq of murine Peyer's patches after one dose of anti-α4β7 antibody or PBS |
| Organism |
Mus musculus |
| Experiment type |
Other
Expression profiling by high throughput sequencing
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| Summary |
Targeting the α4β7-MAdCAM-1 axis with vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined five distinct cohorts of patients with UC (n=83, n=60, n=21, n=31, n=401), to determine the effect of VDZ on the mucosal and peripheral immune system. We found a significant decrease in colonic and ileal naïve B and T cells and circulating gut- homing plasmablasts (β7+) in VDZ-treated patients, pointing to gut-associated lymphoid tissue (GALT) targeting by VDZ. Murine Peyer’s patches (PP) demonstrated a significant loss cellularity associated with reduction in follicular B cells, including a unique population of epithelium-associated B cells, following anti-α4β7 antibody (mAb) administration. Photoconvertible (KikGR) mice demonstrated impaired cellular entry into PPs in anti-α4β7 mAb treated mice. In VDZ-treated, but not anti-tumor necrosis factor-treated UC patients, lymphoid aggregate size was significantly reduced in treatment responders compared to non- responders, with an independent validation cohort further confirming these data. Response to VDZ was associated with a significant decrease of naïve B cells and a reduction in B cell follicle organization in the GALT. Responders had a significant reduction of β7+IgG+ plasmablasts in circulation, as well as IgG+ plasma cells and FcgR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated MOA of α4β7-targeted therapies, with major implications for this therapeutic paradigm in UC, and for the development of new therapeutic strategies.
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| Overall design |
Peyer's patches were isolated from the small inthestine of treated mice and incubated with collagenase D, before mechanical homogenization to obtain a single-cell suspension.
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| Contributor(s) |
Canales-Herrerias P, Uzzan M, Seki A, Mehandru S |
| Citation(s) |
38640252 |
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| Submission date |
Dec 20, 2023 |
| Last update date |
Jun 12, 2024 |
| Contact name |
Darwin D'Souza |
| Organization name |
Human Immune Monitoring Center
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| Department |
ImmunoBio
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| Street address |
1470 Madison Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM7987245 |
PBS-treated and α4β7-treated cells, load 1, GEX |
| GSM7987246 |
PBS-treated and α4β7-treated cells, load 1, HTO |
| GSM7987247 |
PBS-treated and α4β7-treated cells, load 2, GEX |
| GSM7987248 |
PBS-treated and α4β7-treated cells, load 2, HTO |
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| Relations |
| BioProject |
PRJNA1055157 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE251745_PabloCELLPLEX2_raw_matrix.h5ad.gz |
147.4 Mb |
(ftp)(http) |
H5AD |
| GSE251745_PabloCELLPLEX3_raw_matrix.h5ad.gz |
116.8 Mb |
(ftp)(http) |
H5AD |
| GSE251745_readme.txt |
267 b |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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