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Status |
Public on Oct 29, 2018 |
Title |
RNA-seq of Tfh IL21+ single producers and Tfh IL21+ IL10+ double producers |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
During chronic viral infection, the inflammatory function of CD4 T cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this T cell adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T cells during chronic infection. Unexpectedly, our analyses revealed an IL-10-producing population with a robust Tfh-signature. Using IL-10 and IL-21 double-reporter mice, we further demonstrate that IL-10+IL-21+co-producing Tfh cells arise predominantly during chronic but not acute LCMV infection. Importantly, depletion of IL-10+IL-21+co-producing CD4 T cells or deletion of Il10 specifically in Tfh cells resulted in impaired humoral immunity and viral control. Mechanistically, B cell-intrinsic IL-10 signaling was required for sustaining germinal center reactions. Lastly, we demonstrate that IL-27 and type I IFNs differentially regulate the formation of this protective IL-10-producing Tfh subset. Thus, our findings elucidate a critical role for Tfh-derived IL-10 in promoting humoral immunity during persistent viral infection.
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Overall design |
3 samples (Naive, Tfh IL21+ IL10-, Tfh IL21+ IL10+), 2-3 biological replicates per sample
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Contributor(s) |
Cui W, Schauder DM |
Citation(s) |
30487586 |
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Submission date |
Feb 22, 2018 |
Last update date |
Mar 25, 2019 |
Contact name |
Weiguo Cui |
E-mail(s) |
wcui04@gmail.com
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Phone |
312-503-0332
|
Organization name |
Northwestern University
|
Department |
Pathology
|
Lab |
Cui
|
Street address |
303 E Chicago Ave
|
City |
Chicago |
State/province |
IL |
ZIP/Postal code |
60654 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (8)
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This SubSeries is part of SuperSeries: |
GSE111027 |
Single-cell RNA sequencing unveils a unique IL-10-producing T follicular helper subset that sustains humoral immunity during chronic viral infection |
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Relations |
BioProject |
PRJNA435612 |
SRA |
SRP133325 |