Lymphatic Clearance of Immune Cells in Cardiovascular Disease
Abstract
:1. Introduction
2. Immune Cells in the Heart
2.1. Neutrophils: The First Cells to Arrive at the Site of Infarction
2.2. Monocyte/Macrophages: Cells Involved in Both Inflammation and Its Resolution
2.3. Dendritic Cells: Regulators of Immune Tolerance during MI
2.4. T-Lymphocytes: CD4+ Helper T Cells
2.5. T-Lymphocytes: CD8+ Cytotoxic T Cells
2.6. B-Lymphocytes
3. Cardiac Lymphatic Network
3.1. Lymphatic Development in the Embryo
3.2. Cardiac Lymphatic Remodelling Following Myocardial Infarction
3.3. Exit of Immune Cells from the Infarcted Heart—The Role of Cardiac Lymphatics
3.4. Mechanisms of Immune Cell Exit via the Cardiac Lymphatics
4. Lymphangiogenic Therapy Post-MI
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Cell Type | Subtypes | Markers | Timeline [4,5] | Function | KO Effect | References |
---|---|---|---|---|---|---|
Neutrophils | N1 | CD45+CD11b+Ly6C+ Ly6G+CD206− | From Day 1 to day 5 | Clear debris and dead cells. Pro-inflammatory | Neutrophil deletion worsens cardiac function and increases fibrosis * | [6] |
N2 | CD45+CD11b+Ly6C+ Ly6G+CD206+ | From Day 5 | Anti-inflammatory | [7,8] | ||
Monocytes | Inflammatory | CD14+Ly-6Chigh CCR2highCX3CR1low | From the 1st day and peak at day 3–day 5 | Phagocytose and proteolytic activities. Inflammatory | Cardiac Fibrosis Heart Failure | [9,10,11] |
Non-Classical | CD14+Ly-6Clow CCR2lowCX3CR1high | From day 5 onwards | Reparative process: Angiogenesis & ECM deposition | Acute inflammatory reaction 7 days post MI. No long-term differences in scar formation | [10] | |
Macrophages | Residents | CD45+CD11b+ Ly6G–F4/80+ | Present before MI. Quickly replaced by other immune cells | Maintain homeostasis. Recruit monocytes and promote neutrophil extravasation post-MI | Adverse remodelling | [12,13,14,15] |
M1-Like | CD45+ Ly6G–CD11bhigh F4/80+CD206− Ly-6Chigh | Peaks at day 3 | Phagocytose and proinflammatory | High mortality rate. Increase remodelling | [16,17] | |
M2-Like | CD45+ Ly6G–CD11blow F4/80+CD206+ Ly-6Clow | Appear 3 to 5 days post-MI and onwards | Anti-inflammatory. Promote cell proliferation, angiogenesis, and ECM production | Cardiac rupture | [18,19] | |
Dendritic Cells | cDC | CD45+MHCII+ CD11c+Zbtb46+ | Infiltrate at day 1 and peak at day 5 * | [20] | ||
pDC | CD45+MHCII+ CD11c+BDCA2+ | Antigen Presentation to T-Lymphocytes * | Improves cardiac function & attenuation of inflammation | [21,22] * | ||
toDC | CD45+MHCIIlow CD11c+ | Activate Tregs | Total DC depletion promotes inflammation and increases cardiac rupture * | [23,24] | ||
T- Lymphocytes | CD4+ | CD45+CD11b− CD3+CD4+ | Infiltrate at day 1 and peak at day 7 | Produce pro-inflammatory cytokines | Increase pro-inflammatory monocytes. Impair collagen matrix formation | [25,26] |
Tregs | CD45+CD11b− CD3+ CD4+CD25+FoxP3+ | Infiltrate at day 1 and peak at day 7 | Promote inflammatory-to-reparative macrophage | Cardiac inflammation | [27,28,29] | |
CD8+ | CD45+CD11b− CD3+CD8+ | Gradually increase post-MI | Removal of necrotic tissue. Cytotoxic effect | Infarct size and fibrosis decreased. Heart function improved but cardiac rupture | [30,31] | |
B- Lymphocytes | N/A | CD45+CD11b− CD3−CD19+ | Peaks at Day 5–7 | Monocyte mobilization Sustain myocardial inflammation | Reduce infarct size and improve cardiac function | [32,33,34] |
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Ravaud, C.; Ved, N.; Jackson, D.G.; Vieira, J.M.; Riley, P.R. Lymphatic Clearance of Immune Cells in Cardiovascular Disease. Cells 2021, 10, 2594. https://doi.org/10.3390/cells10102594
Ravaud C, Ved N, Jackson DG, Vieira JM, Riley PR. Lymphatic Clearance of Immune Cells in Cardiovascular Disease. Cells. 2021; 10(10):2594. https://doi.org/10.3390/cells10102594
Chicago/Turabian StyleRavaud, Christophe, Nikita Ved, David G. Jackson, Joaquim Miguel Vieira, and Paul R. Riley. 2021. "Lymphatic Clearance of Immune Cells in Cardiovascular Disease" Cells 10, no. 10: 2594. https://doi.org/10.3390/cells10102594