期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00400
关键词
interleukin-10; macrophages; inflammation; colitis; therapy
类别
资金
- Portuguese Foundation for Science and Technology (FCT) [SFRIl/BD/84704/2012]
- Norte Portugal Regional Operational Programme (NORTE) under the PORTUGAL Partnership Agreement through the European Regional Development Fund (FEDER) [Norte-01-0145-FEDER-000012]
- FCT-ANR [FCTANR/BIM-MEC/0007/2013]
- Horizon EU Framework Program Research and Innovation Programme [BM1404]
- Northern Portugal Regional Operational Programme (NORTE) under the Portugal Partnership Agreement through the European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]
- Northern Portugal Regional Operational Programme (NORTE) under the Portugal Partnership Agreement through FEDER [NORTE-01-0145-FEDER-000023]
- FEDER through the Competitiveness Factors Operational Programme (COMPETE)
- National funds through the Foundation for Science and Technology (FCT) [POCI-01-0145-FEDER-007038]
- ANR through the project MYELOTEN [ANR-13-ISV1-0003-01]
- Agence Nationale de la Recherche (ANR) [ANR-13-ISV1-0003] Funding Source: Agence Nationale de la Recherche (ANR)
- Fundação para a Ciência e a Tecnologia [FCT-ANR/BIM-MEC/0007/2013] Funding Source: FCT
Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据