Subcutaneous injection of dendritic cells aggravates atherosclerosis in ApoE‑knockout mice by activation of TLR4

Ye,Zhishuai; Jin,Mingyu; Wang,Shujing; Zhang,Jianing; Song,Xiantao; Huang,Rongchong

doi:10.3892/mmr.2017.7339

Subcutaneous injection of dendritic cells aggravates atherosclerosis in ApoE‑knockout mice by activation of TLR4

Authors:
- Zhishuai Ye
- Mingyu Jin
- Shujing Wang
- Jianing Zhang
- Xiantao Song
- Rongchong Huang
View Affiliations

Affiliations: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, College of Life Sciences and Pharmacy, Dalian University of Technology, Dalian, Liaoning 116027, P.R. China, Department of Cardiology, Capital Medical University Affiliated Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, P.R. China
Published online on: August 23, 2017 https://doi.org/10.3892/mmr.2017.7339
Pages: 6041-6049
Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Dendritic cells (DCs) are specialized antigen‑presenting cells which are important in immune diseases, in particular atherosclerosis, a chronic inflammatory disease, however their role in atherosclerosis‑associated immunity is unclear. To evaluate the role of DCs in atherosclerosis, exogenous bone marrow‑derived DCs were transferred into ApoE‑/‑ mice in the present study. The extent of disease was measured in the aorta and was compared with mice treated with phosphate‑buffered saline (PBS) or left untreated and fed a western diet. Mice receiving exogenous DCs demonstrated significantly larger atherosclerotic lesions compared with the mice treated with PBS, with increasing numbers of mature DCs in circulation and enhanced DC infiltration into plaque lesions, in addition to activation of circulating inflammatory components and atherosclerotic lesions. Furthermore, it was demonstrated that exogenous DCs upregulated the expression of Toll‑like receptor 4 (TLR4) on DCs, which may be an important mechanism to activate DCs and aggravate atherosclerosis. Therefore the present study concluded that exogenous DCs may induce maturation of endogenous DCs via upregulation of TLR4, further increasing the inflammatory response and accelerating atherosclerosis.

View Figures

View References

1	Libby P: Inflammation in atherosclerosis. J Associat Physicians India. 48:265–266. 2012.
2	Ross R: Atherosclerosis-an inflammatory disease. N Engl J Med. 340:115–126. 1999. View Article : Google Scholar : PubMed/NCBI
3	Banchereau J and Steinman RM: Dendritic cells and the control of immunity. Nature. 392:245–252. 1998. View Article : Google Scholar : PubMed/NCBI
4	Bobryshev YV and Watanabe T: Subset of vascular dendritic cells transforming into foam cells in human atherosclerotic lesions. Cardiovasc Pathol. 6:321–331. 1997. View Article : Google Scholar : PubMed/NCBI
5	Chistiakov DA, Sobenin IA, Orekhov AN and Bobryshev YV: Dendritic cells in atherosclerotic inflammation: The complexity of functions and the peculiarities of pathophysiological effects. Front Physiol. 5:1962014. View Article : Google Scholar : PubMed/NCBI
6	Choi J, Do Y, Cheong C, Koh H, Boscardin SB, Oh YS, Bozzacco L, Trumpfheller C, Park CG and Steinman RM: Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. J Exp Med. 206:497–505. 2009. View Article : Google Scholar : PubMed/NCBI
7	Koltsova EK and Ley K: How dendritic cells shape atherosclerosis. Trends Immunol. 32:540–547. 2011. View Article : Google Scholar : PubMed/NCBI
8	Mellman I and Steinman RM: Dendritic cells: Specialized and regulated antigen processing machines. Cell. 106:255–258. 2001. View Article : Google Scholar : PubMed/NCBI
9	Chen L: Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol. 4:336–347. 2004. View Article : Google Scholar : PubMed/NCBI
10	Akira S and Takeda K: Toll-like receptor signalling. Nat Rev Immunol. 4:499–511. 2004. View Article : Google Scholar : PubMed/NCBI
11	Son YI, Egawa S, Tatsumi T, Redlinger RE Jr, Kalinski P and Kanto T: A novel bulk-culture method for generating mature dendritic cells from mouse bone marrow cells. J Immunol Methods. 262:145–157. 2002. View Article : Google Scholar : PubMed/NCBI
12	Paulson KE, Zhu SN, Chen M, Nurmohamed S, Jongstra-Bilen J and Cybulsky MI: Resident intimal dendritic cells accumulate lipid and contribute to the initiation of atherosclerosis. Circ Res. 106:383–390. 2010. View Article : Google Scholar : PubMed/NCBI
13	Rong JX, Shapiro M, Trogan E and Fisher EA: Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc Natl Acad Sci USA. 100:13531–13536. 2003; View Article : Google Scholar : PubMed/NCBI
14	Ling GS, Bennett J, Woollard KJ, Szajna M, Fossati-Jimack L, Taylor PR, Scott D, Franzoso G, Cook HT and Botto M: Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages. Nat Commun. 5:30392014. View Article : Google Scholar : PubMed/NCBI
15	Chávez-Sánchez L, Espinosa-Luna JE, Chávez-Rueda K, Legorreta-Haquet MV, Montoya-Díaz E and Blanco-Favela F: Innate immune system cells in atherosclerosis. Arch Med Res. 45:1–14. 2014. View Article : Google Scholar : PubMed/NCBI
16	Macritchie N, Grassia G, Sabir SR, Maddaluno M, Welsh P, Sattar N, Ialenti A, Kurowska-Stolarska M, McInnes IB, Brewer JM, et al: Plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 32:2569–2579. 2012. View Article : Google Scholar : PubMed/NCBI
17	Weeks MF, Rampersad RR and Liu P: Dendritic cells and macrophages contribute differently to the initiation of atherosclerosis. Circulation. 126:A157152012.
18	Hansson GK and Hermansson A: The immune system in atherosclerosis. Nat Immunol. 12:204–212. 2011. View Article : Google Scholar : PubMed/NCBI
19	Mempel TR, Henrickson SE and Von Andrian UH: T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature. 427:154–159. 2004. View Article : Google Scholar : PubMed/NCBI
20	Gautier EL, Huby T, Saint-Charles F, Ouzilleau B, Pirault J, Deswaerte V, Ginhoux F, Miller ER, Witztum JL, Chapman MJ and Lesnik P: Conventional dendritic cells at the crossroads between immunity and cholesterol homeostasis in atherosclerosis. Circulation. 119:2367–2375. 2009. View Article : Google Scholar : PubMed/NCBI
21	Glass CK and Witztum JL: Atherosclerosis: The road ahead. Cell. 104:503–516. 2001. View Article : Google Scholar : PubMed/NCBI
22	Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori M, Katsumata T, et al: MafB promotes atherosclerosis by inhibiting foam-cell apoptosis. Nat Commun. 5:31472014. View Article : Google Scholar : PubMed/NCBI
23	Liu SW, Qiao SB, Yuan JS and Liu DQ: Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans. Clin Endocrinol (Oxf). 71:202–207. 2009. View Article : Google Scholar : PubMed/NCBI
24	de Kleijn D and Pasterkamp G: Toll-like receptors in cardiovascular diseases. Cardiovasc Res. 60:58–67. 2003. View Article : Google Scholar : PubMed/NCBI
25	Hayashi C, Papadopoulos G, Gudino CV, Weinberg EO, Barth KR, Madrigal AG, Chen Y, Ning H, LaValley M, Gibson FC III, et al: Protective role for TLR4 signaling in atherosclerosis progression as revealed by infection with a common oral pathogen. J Immunol. 189:3681–3688. 2012. View Article : Google Scholar : PubMed/NCBI
26	Subramanian M, Thorp E, Hansson GK and Tabas I: Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs. J Clin Invest. 123:179–188. 2013. View Article : Google Scholar : PubMed/NCBI
27	Alroqi FJ and Chatila TA: T regulatory cell biology in health and disease. Curr Allergy Asthma Rep. 16:272016. View Article : Google Scholar : PubMed/NCBI
28	Sakaguchi S, Yamaguchi T, Nomura T and Ono M: Regulatory T cells and immune tolerance. Cell. 133:775–787. 2008. View Article : Google Scholar : PubMed/NCBI