Batf3-dependent CD8α+ Dendritic Cells Aggravates Atherosclerosis via Th1 Cell Induction and Enhanced CCL5 Expression in Plaque Macrophages
| Autor: | Wengang Song, Xueyan Liu, Hua Tian, Shutong Yao, Hua Tang, Wei Duan, Hao He, Guangming Zhu, Shuying Yi, Yalin Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine Cell lcsh:Medicine Inflammation General Biochemistry Genetics and Molecular Biology CCL5 Lesion 03 medical and health sciences Th1 cells CD8α+ DCs medicine Transcription factor lcsh:R5-920 biology lcsh:R Batf3 General Medicine medicine.disease Acquired immune system Atherosclerosis Molecular biology 030104 developmental biology medicine.anatomical_structure Immunology biology.protein medicine.symptom lcsh:Medicine (General) Infiltration (medical) |
| Zdroj: | EBioMedicine, Vol 18, Iss C, Pp 188-198 (2017) |
| ISSN: | 2352-3964 |
| Popis: | Dendritic cells (DCs) play an important role in controlling T cell-mediated adaptive immunity in atherogenesis. However, the role of the basic leucine zipper transcription factor, ATF-like 3 (Batf3)-dependent CD8α+ DC subset in atherogenesis remains unclear. Here we show that Batf3−/− Apoe−/− mice, lacking CD8α+ DCs, exhibited a significant reduction in atherogenesis and T help 1 (Th1) cells compared with Apoe−/− controls. Then, we found that CD8α+ DCs preferentially induce Th1 cells via secreting interleukin-12 (IL-12), and that the expression of interferon-gamma (IFN-γ)or chemokine (C-C motif) ligand 5 (CCL5) in aorta were significantly decreased in Batf3−/− Apoe−/− mice. We further demonstrated that macrophages were the major CCL5-expressing cells in the plaque, which was significantly reduced in Batf3−/− Apoe−/− mice. Furthermore, we found CCL5 expression in macrophages was promoted by IFN-γ. Finally, we showed that Batf3−/− Apoe−/− mice displayed decreased infiltration of leukocytes in the plaque. Thus, CD8α+ DCs aggravated atherosclerosis, likely by inducing Th1 cell response, which promoted CCL5 expression in macrophages and increased infiltration of leukocytes and lesion inflammation. |
| Databáze: | OpenAIRE |
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