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| Status |
Public on Jun 25, 2014 |
| Title |
DOCK8 regulates protective immunity by controlling the function and survival of RORγt+ ILCs |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Retinoic-acid receptor-related orphan receptor-γt-positive (RORγt+) innate lymphoid cells (ILCs) produce interleukin (IL)-22 and IL-17, which are critical for protective immunity against enteric pathogens. The molecular mechanism underlying the development and survival of RORγt+ ILCs is not thoroughly understood. Here we show that Dedicator of cytokinesis 8 (DOCK8), a scaffolding protein involved in cytoskeletal rearrangement and cell migration, is essential for the protective immunity against Citrobacter rodentium. A comparative RNA sequencing-based analysis reveals an impaired induction of antimicrobial peptides in the colon of DOCK8-deficient mice, which correlates with high susceptibility to infection and a very low number of IL-22-producing RORγt+ ILCs in their GI tract. Furthermore, DOCK8-deficient RORγt+ ILCs are less responsive to IL-7 mediated signaling, more prone to apoptosis and produce less IL-22 due to a defect in IL-23-mediated STAT3 phosphorylation. Our studies reveal an unsuspected role of DOCK8 for the function, generation and survival of RORγt+ ILCs.
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| Overall design |
Control and DOCK8 KO mice were infected with 2X109 CFU of Citrobacter rodentium and day 8 post infection mice were sacrificed and their colons were harvested (n=5) . Total RNA was purified from the infected colons with RNeasy mini kit (Qiagen). RNA sequencing was performed (pooled RNA sample from five mice in each group) at Genomic Core Facility Southwestern Medical Center, University of Texas.
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| Contributor(s) |
Singh AK, Oukka M |
| Citation(s) |
25091235 |
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| Submission date |
Jun 24, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Akhilesh K Singh |
| Organization name |
Seattle Childrens Research Institute
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| Department |
Center for Immunity and Immunotherapies
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| Lab |
Mohamed Oukka Lab
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| Street address |
1900, 9th AVE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98101 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA253372 |
| SRA |
SRP043526 |
