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Series GSE97571 Query DataSets for GSE97571
Status Public on Aug 31, 2017
Title Selective induction of homeostatic Th17 cells in the murine intestine by cholera toxin interacting with the microbiota
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease (IBD) and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype, i.e., they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL/6.IgA-/- mice compared to wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CTB-specific serum IgG response in C57BL/6.IgA-/- mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria (SFB) in the small intestine of C57BL/6.IgA-/- mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA-/- and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by SFB but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expressions of a panel of immune regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a non-pathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.
Overall design Transcriptome analysis of CD4+hCD2+ cells of CT Immunized IgA-/- mice, CD4+hCD2+ cells of IgA-/- mice, CD4+CD25- cells from spleen of WT B6 mice, naïve CD4+CD25-, Th17 with IL-23+IL-1b.
Contributor(s) Zhao Q, Charles EO, Kolde R
Citation(s) 28539431
Submission date Apr 10, 2017
Last update date May 15, 2019
Contact name Raivo Kolde
Organization name Broad Institute
Street address 415 Main St
City Cambridge
ZIP/Postal code 02142
Country USA
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (8)
GSM2572280 CD4+hCD2+ cells of CT Immunized IgA-/- mice (CE1)
GSM2572281 CD4+hCD2+ cells of CT Immunized IgA-/- mice (CE2)
GSM2572282 CD4+hCD2+ cells of IgA-/- mice (CE6)
BioProject PRJNA382350
SRA SRP103764

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Supplementary file Size Download File type/resource
GSE97571_2017-04-07_ce_counts.txt.gz 220.8 Kb (ftp)(http) TXT
GSE97571_2017-04-07_ce_norm.txt.gz 500.1 Kb (ftp)(http) TXT
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