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| Status |
Public on Mar 27, 2016 |
| Title |
Global genome expression analysis of lamina propria derived WT and Nlrp6-/- Ly6C-hi inflammatory monocytes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Nlrp6-/- lamina propria Ly6C-hi monocytes in response to AOM/DSS have deficient TNFα production, but increased production of other pro-inflammatory cytokines as compared to WT
NLRP6 is a member of the Nod-like receptor family, whose members are involved in the recognition of microbes and/or tissue injury. NLRP6 was previously demonstrated to regulate the production of IL-18 and is important for protecting mice against chemically-induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms by which NLRP6 reduces susceptibility to colonic inflammation remain unclear. Here, we determined that NLRP6 expression is specifically upregulated in Ly6Chi inflammatory monocytes that infiltrate into the colon during dextran sulfate sodium (DSS)-induced inflammation. Adoptive transfer of WT Ly6Chi inflammatory monocytes into Nlrp6-/- mice was sufficient to protect them from mortality, significantly reducing intestinal permeability and damage. NLRP6-deficient inflammatory monocytes were specifically defective in TNFα production, which was important for reducing DSS-induced mortality and dependent on autocrine IL-18 signaling by inflammatory monocytes. Our data reveal a previously unappreciated role for NLRP6 in inflammatory monocytes, which are recruited during intestinal injury to promote barrier function and limit bacteria-driven inflammation. This study also highlights the importance of early cytokine responses, particularly NLRP6-dependent and IL-18-dependent TNFα production in preventing chronic dysregulated inflammation.
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| Overall design |
Ly6Chi monocytes were sorted from lamina propria of WT or Nlrp6-/- mice at day 10 of AOM/2%DSS. RNA was extracted and hybridized to the mouse 2.1 ST array.
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| Contributor(s) |
Chen GY, Seregin SS |
| Citation(s) |
27353251 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| F32 CA200144 |
Understanding Nlrp6 function in inflammatory monocytes during inflammation and tumorigenesis |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
SEREGIN |
| R01 CA166879 |
Regulation of intestinal inflammation and tumorigenesis by Nlrp6 |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
CHEN |
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| Submission date |
Mar 26, 2016 |
| Last update date |
Mar 08, 2018 |
| Contact name |
Sergey Seregin |
| E-mail(s) |
seregin@umich.edu
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| Organization name |
University of Michigan
|
| Street address |
1150 E Medical Center Drive
|
| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA316515 |
