Flt3 Signaling-Dependent Dendritic Cells Protect against Atherosclerosis
| Autor: | Durga Bhavani Dandamudi, Saurabh Mehandru, Goo Taeg Oh, Chae Gyu Park, In Hyuk Jung, Ralph M. Steinman, Jae-Hoon Choi, Ji Young Yoo, Cheolho Cheong, Klara Velinzon, Anthony Rodriguez |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_treatment
CD14 Immunology CD11c chemical and pharmacologic phenomena 030204 cardiovascular system & hematology Monocytes Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Antigens CD medicine.artery medicine Animals Immunology and Allergy Aorta 030304 developmental biology Mice Knockout Mice Inbred BALB C 0303 health sciences biology Macrophage Colony-Stimulating Factor Macrophages Membrane Proteins FOXP3 hemic and immune systems Dendritic Cells Atherosclerosis Mice Inbred C57BL Cytokine Infectious Diseases Gene Expression Regulation fms-Like Tyrosine Kinase 3 Integrin alpha M cardiovascular system biology.protein Leukocyte Reduction Procedures Signal Transduction |
| Zdroj: | Immunity. 35(5):819-831 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2011.09.014 |
| Popis: | Early events in atherosclerosis occur in the aortic intima and involve monocytes that become macrophages. We looked for these cells in the steady state adult mouse aorta, and surprisingly, we found a dominance of dendritic cells (DCs) in the intima. In contrast to aortic adventitial macrophages, CD11c(+)MHC II(hi) DCs were poorly phagocytic but were immune stimulatory. DCs were of two types primarily: classical Flt3-Flt3L signaling-dependent, CD103(+)CD11b(-) DCs and macrophage-colony stimulating factor (M-CSF)-dependent, CD14(+)CD11b(+)DC-SIGN(+) monocyte-derived DCs. Both types expanded during atherosclerosis. By crossing Flt3(-/-) to Ldlr(-/-) atherosclerosis-prone mice, we developed a selective and marked deficiency of classical CD103(+) aortic DCs, and they were associated with exacerbated atherosclerosis without alterations in blood lipids. Concomitantly, the Flt3(-/-)Ldlr(-/-) mice had fewer Foxp3(+) Treg cells and increased inflammatory cytokine mRNAs in the aorta. Therefore, functional DCs are dominant in normal aortic intima and, in contrast to macrophages, CD103(+) classical DCs are associated with atherosclerosis protection. |
| Databáze: | OpenAIRE |
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