期刊
JOURNAL OF IMMUNOLOGY
卷 184, 期 9, 页码 4819-4826出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0903063
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资金
- Ministry of Education, Science and Culture of Japan [C: 17590888, C: 13670659, C: 15590901, B: 19390156]
- Mitsubishi Pharma Research Foundation, Japan
- Grants-in-Aid for Scientific Research [17590888, 15590901, 19390156, 13670659, 21659400] Funding Source: KAKEN
Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recent studies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19(Cre)/hVEGF-A(fl)) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses. The Journal of Immunology, 2010, 184: 4819-4826.
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