期刊
ONCOTARGET
卷 7, 期 26, 页码 39256-39269出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9684
关键词
PAMPs; DAMPs; draining lymph node; CD1a+interdigitating DCs; CD1c+DCs; Pathology Section
资金
- AIRC (Associazione Italiana Ricerca sul Cancro)
- Fondazione Berlucchi
- MIUR (Ministero dell'Istruzione Universita e Ricerca)
- Fondazione Cariplo
- FIRC (Fondazione Italiana Ricerca sul Cancro)
- ERC - NOW ERC from Cariplo Foundation [2014-2256]
- Regione Lombardia
- IAP (Interuniversity Attraction Poles) [7-40]
Lymph node expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Previous work in mice has shown that this process depends on the presence of VEGF-A produced by B cells, macrophages and stromal cells. In humans, however, the cell types and the mechanisms regulating the intranodal production of VEGF-A remain elusive. Here we show that CD11c+ cells represent the main VEGF-A-producing cell population in human reactive secondary lymphoid organs. In addition we find that three transcription factors, namely CREB, HIF-1 alpha and STAT3, regulate the expression of VEGF-A in inflamed DCs. Both HIF-1 alpha and STAT3 are activated by inflammatory agonists. Conversely, CREB phosphorylation represents the critical contribution of endogenous or exogenous PGE(2). Taken together, these results propose a crucial role for DCs in lymph node inflammatory angiogenesis and identify novel potential cellular and molecular targets to limit inflammation in chronic diseases and tumors.
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