The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View
Abstract
:1. Introduction
2. Estrogens
Estrogen Receptors
3. Estrogen Effects on the Immune System: Focus on MS
3.1. Innate Immune Cells
3.2. T Cells
3.3. B Cells
4. Estrogens Modulate the T Helper Epigenome in MS
5. Estrogens as a Potential MS Therapy
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Cell Type | Effect in Immune System | References | Effect in EAE/MS | References |
---|---|---|---|---|
Neutrophils | ↓ TNF-α, IL-6, IL-1β | [113] | ||
↓ Chemotaxis (iNOS, CINC-1, CINC-2β, CINC-3) | [114] | |||
Macrophages | ↓ TNF-α, IL-6, IL-1β | [115] | ||
↓ iNOS and T-bet | [75] | ↓ iNOS and T-bet | [75] | |
↑ IL-10 | [75] | ↑ IL-10 | [75] | |
Dendritic Cells | ↑ Differentiation (IL-8, and CCL2) | [116,117] | ↑ Differentiation (IL-8, and CCL2) | [116] |
↓ iNOS, T-bet, TNF-α, IFN-γ, IL-12, PD-L1, PD-L2 | [75,116,117,118] | ↓ iNOS, T-bet, TNF-α, IFN-γ, IL-12, PD-L1, PD-L2 | [75,116,118] | |
↑ IL-10 | [75,117] | ↑ IL-10 | [75] | |
↑ IL-6, IFN-γ | [119] | |||
Microglia | ↑ M2 polarization | [77,120] | ↑ M2 polarization | [77] |
↓ Activation | [76] | ↓ Activation | [76] | |
↓ NF-kB, IL-1β | [73] | |||
↑ IL-10 | [73] | |||
NK | ↓ Cytotoxic activity | [121] | ||
↑ Activation of CD3+CD56+CD8+ cells | [122] | ↑ Activation of CD3+CD56+CD8+ cells | [122] | |
T cells | ↑ Treg/Th2 | [120,123] | ↑ Treg/Th2 | [123,124] |
↓ Th17/Th1 | [123,125] | ↓ Th17/Th1, T cell infiltration in CNS | [123,125] | |
↓ TFH cell response | [126] | ↓ TFH cell response | [126] | |
↓ T CD8+ cells | [120] | |||
↑↓ IFN-γ | [78,79,80,81,82,83] | ↓ IFN-γ | [79,80,81,83,127] | |
↑↓ TNF-α | [81,98,123] | ↓ TNF-α | [81,98,123] | |
↑ IL-10, IL-4, TGF-β | [83,84] | ↑ IL-10, IL-4, TGF-β | [83] | |
↓ IL-17 and IL-23 | [123] | ↓ IL-17 and IL-23 | [123,127] | |
↓ NF-kB, iNOS | [76] | ↓ NF-kB, iNOS | [76] | |
↑ PD-1, CTLA4, FOXP3, GATA3 | [83,90,92,93] | ↑ PD-1, CTLA4, FOXP3, GATA3 | [83,90,92,93] | |
↓ RORC, T-bet | [90,123] | ↓ RORC, T-bet | [90,123] | |
B cells | ↑ IL-10 | [77] | ↑ IL-10 | [77] |
↑ PD-L1 | [110,111,125] | ↑ PD-L1 | [110,111,125] |
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Maglione, A.; Rolla, S.; Mercanti, S.F.D.; Cutrupi, S.; Clerico, M. The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View. Cells 2019, 8, 1280. https://doi.org/10.3390/cells8101280
Maglione A, Rolla S, Mercanti SFD, Cutrupi S, Clerico M. The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View. Cells. 2019; 8(10):1280. https://doi.org/10.3390/cells8101280
Chicago/Turabian StyleMaglione, Alessandro, Simona Rolla, Stefania Federica De Mercanti, Santina Cutrupi, and Marinella Clerico. 2019. "The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View" Cells 8, no. 10: 1280. https://doi.org/10.3390/cells8101280