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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 13, 2022 |
| Title |
Apyrase-mediated amplification of secretory IgA promotes intestinal homeostasis |
| Platform organism |
Mus musculus |
| Sample organism |
Mus |
| Experiment type |
Expression profiling by array
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| Summary |
Morphogenesis of epithelial tissues relies on the precise developmental control of cell polarity and architecture. In the early Drosophila embryo, the primarSecretory IgA (SIgA) interaction with commensal bacteria regulates the composition and function of the microbiota, contributing to gut ecosystem homeostasis. However, mechanisms regulating the reciprocal control of microbiota and SIgA are not defined. Bacteria-derived ATP limits T follicular helper (Tfh) cells activity in the Peyer’s patches (Pps) of the small intestine via the P2X7 receptor and thereby SIgA generation. Here we show that inhibition of bacteria derived ATP signaling by delivery of the ATP-degrading enzyme apyrase to the intestine results in the amplification of the SIgA repertoire. The enhanced breadth of SIgA in mice colonized with apyrase-releasing E. Coli conditioned topographical distribution of bacteria and expression of genes involved in metabolic versus immune functions in the intestinal epithelium. SIgA mediated conditioning of bacteria and enterocyte function was also reflected by selective differences in nutrients absorption in mice colonized with apyrase expressing bacteria. Hydrolysis of bacteria derived ATP was particularly helpful in restoring intestinal homeostasis via SIgA in antibiotics induced dysbiosis. Administration of apyrase expressing bacteria attenuated intestinal barrier impairment, glucose metabolism perturbation and susceptibility to infection by enteric pathogens induced by antibiotic treatments. Therefore, microbiota derived ATP regulates SIgA, and amplification of SIgA response by apyrase can be leveraged to restore intestinal fitness in dysbiotic conditions.y epithelium forms during cellularisation, following a tightly controlled genetic programme where specific sets of genes are up-regulated. Some of them, for instance, control membrane invagination between the nuclei anchored at the apical surface of the syncytium.
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| Overall design |
We performed genome-wide expression profiling of small intestinal epithelium from GF mice colonized with E. colipApyr or E. colipBAD28. To evaluate the effect of bacteria-derived eATP on the epithelial transcriptional activity independently of SIgA coating of E. Coli, we performed the same analysis in epithelial cells isolated from gnotobiotic E. colipApyr or E. colipBAD28 C57BL/6 Igh-J-/- mice, which carry a deletion in the J segment of the Ig heavy chain locus and therefore are devoid of immunoglobulins.
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| Contributor(s) |
Peruzza L, Strati F, Grassi F |
| Citation(s) |
35858559 |
| Submission date |
May 20, 2022 |
| Last update date |
Oct 13, 2022 |
| Contact name |
Fabio Grassi |
| E-mail(s) |
fabio.grassi@irb.usi.ch
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| Organization name |
Institute for Research in Biomedicine
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| Street address |
Via Francesco Chiesa 5
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| City |
Bellinzona |
| ZIP/Postal code |
6500 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (23)
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| GSM6171927 |
Mouse WT, pBAD, R1285_8 |
| GSM6171928 |
Mouse Jh, pBAD, R1285_11 |
| GSM6171929 |
Mouse Jh, pBAD, R1285_12 |
| GSM6171930 |
Mouse Jh, pBAD, R1285_13 |
| GSM6171931 |
Mouse Jh, pBAD, R1285_14 |
| GSM6171932 |
Mouse Jh, pBAD, R1285_15 |
| GSM6171933 |
Mouse WT, pHND10, R1285_16 |
| GSM6171934 |
Mouse WT, pHND10, R1285_18 |
| GSM6171935 |
Mouse WT, pHND10, R1285_19 |
| GSM6171936 |
Mouse WT, pHND10, R1285_20 |
| GSM6171937 |
Mouse Jh, R1285_21 |
| GSM6171938 |
Mouse Jh, R1285_22 |
| GSM6171939 |
Mouse Jh, R1285_23 |
| GSM6171940 |
Mouse Jh, R1285_24 |
| GSM6171941 |
Mouse Jh, R1285_25 |
| GSM6171942 |
Mouse WT, pBAD, R1318_1 |
| GSM6171943 |
Mouse WT, pBAD, R1318_2 |
| GSM6171944 |
Mouse WT, pBAD, R1318_3 |
| GSM6171945 |
Mouse WT, pBAD, R1318_4 |
| GSM6171946 |
Mouse WT, pBAD, R1318_5 |
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| Relations |
| BioProject |
PRJNA840855 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE203433_RAW.tar |
22.5 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE203433_RMA_Signals.xlsx |
4.7 Mb |
(ftp)(http) |
XLSX |
| Processed data are available on Series record |
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