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| Status |
Public on Jan 13, 2020 |
| Title |
B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Short-chain fatty acids (SCFAs) butyrate and propionate are metabolites from dietary fibers fermentation by gut microbiota that can affect differentiation or functions of T cells, macrophages and dendritic cells. We show here that these SCFAs directly impact B cells to modulate in a dose-dependent fashion AID and Blimp1 expression, class-switch DNA recombination, somatic hypermutation and plasma cell differentiation, thereby impairing, through B cell-intrinsic activity, local (intestinal) and systemic T-dependent and T-independent antibody responses. In human and mouse B cells, butyrate and propionate upregulate select miRNAs that target Aicda and Prdm1 mRNA-3’UTRs through epigenetic inhibition of histone deacetylation of the respective miRNA host genes. Further, they modulate B cell Aicda and Prdm1 by acting as HDAC inhibitors, not as energy substrate or through GPR-engagement signaling. Finally, butyrate and propionate epigenetic impact on B cells extends to inhibition of autoantibody production and autoimmunity in lupus MRL/Faslpr/lpr and NZB/WF1 mice.
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| Overall design |
Analysis of the mRNA and micrRNA expression profiles in human B cells stimulated with CD154 plus IL-4 and IL-21 in the presence of nil or short-chain fatty acid butyrate
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| |
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| Contributor(s) |
Casali P, Zan H, Chen Y, Mohammad TA |
| Citation(s) |
31896754 |
| |
| Submission date |
Nov 07, 2019 |
| Last update date |
Jan 14, 2020 |
| Contact name |
Yidong Chen |
| E-mail(s) |
[email protected]
|
| Phone |
2105629163
|
| Organization name |
UT Health Science Center at San Antonio
|
| Department |
Population Health Sciences
|
| Street address |
8403 Floyd Curl Drive, MSC 7784
|
| City |
San Antonio |
| State/province |
Texas |
| ZIP/Postal code |
78229 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA588290 |
| SRA |
SRP229120 |
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