| Title |
Expression of Blimp-1 in Dendritic Cells Modulates the Innate Inflammatory Response in Dextran Sodium Sulfate-Induced Colitis
|
|---|---|
| Published in |
Molecular Medicine, December 2014
|
| DOI | 10.2119/molmed.2014.00231 |
| Pubmed ID | |
| Authors |
Sun Jung Kim, Jordan Goldstein, Kimberly Dorso, Miriam Merad, Lloyd Mayer, James M. Crawford, Peter K. Gregersen, Betty Diamond |
| Abstract |
A single nucleotide polymorphism of PRDM1, the gene encoding Blimp-1, is strongly associated with inflammatory bowel disease. Here, we demonstrate that Blimp-1 in CD103+ dendritic cells (DCs) critically contributes to the regulation of macrophage homeostasis in the colon. Dextran sodium sulfate (DSS)-exposed Blimp-1(cko) mice with a deletion of Blimp-1 in CD103+ DCs and CD11c(hi) macrophages exhibited severe inflammatory symptoms, pronounced weight loss, high mortality, robust infiltration of neutrophils in epithelial regions of the colon, an increased expression of proinflammatory cytokines, and a significant decrease in CD103+ DCs in the colon compared to DSS exposed wild type (WT) mice. Purified colonic macrophages from Blimp-1(cko) mice expressed increased levels of matrix metalloproteinase 8, 9 and 12 mRNA. WT macrophages co-cultured with colonic DCs but not bone marrow derived DCs from Blimp-1(cko) produced increased MMPs in an IL-1β and IL-6 dependent manner. Treatment of Blimp-1(cko) mice with anti-IL-1β and anti-IL-6 abrogated the exaggerated clinical response. Overall, these data demonstrate that Blimp-1 expression in DCs can alter an innate inflammatory response by modulating the activation of myeloid cells. This is a novel mechanism of contribution of Blimp-1 for the pathogenesis of inflammatory bowel diseases, implicating another therapeutic target for the development of inflammatory bowel disease. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 4% |
| United States | 1 | 4% |
| Unknown | 26 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 39% |
| Researcher | 5 | 18% |
| Student > Bachelor | 3 | 11% |
| Student > Doctoral Student | 2 | 7% |
| Professor | 2 | 7% |
| Other | 3 | 11% |
| Unknown | 2 | 7% |
| Readers by discipline | Count | As % |
|---|---|---|
| Immunology and Microbiology | 7 | 25% |
| Biochemistry, Genetics and Molecular Biology | 5 | 18% |
| Medicine and Dentistry | 4 | 14% |
| Agricultural and Biological Sciences | 3 | 11% |
| Engineering | 2 | 7% |
| Other | 2 | 7% |
| Unknown | 5 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 April 2015.
All research outputs
#14,812,046
of 22,805,349 outputs
Outputs from Molecular Medicine
#780
of 1,136 outputs
Outputs of similar age
#185,851
of 331,382 outputs
Outputs of similar age from Molecular Medicine
#6
of 16 outputs
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