| Autor: |
Chatterjee, Piyali, Chiasson, Valorie L., Seerangan, Geetha, De Guzman, Eugene, Milad, Moheb, Bounds, Kelsey R., Gasheva, Olga, Tobin, Richard P., Hatahet, Mohamad, Kopriva, Shelley, Jones, Kathleen A., Newell-Rogers, M. Karen, Mitchell, Brett M. |
| Zdroj: |
Clinical Science; Aug2017, Vol. 131 Issue 15, p2047-2058, 12p, 6 Graphs |
| Abstrakt: |
Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia (PE); however, the molecular mechanisms involved are unknown.We tested the hypothesis that Toll-like receptor (TLR) activation induces major histocompatibility complex (MHC) class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause PE-like features in mice. Treatment with VG1177, a competitive antagonist peptide for CLIP in the groove of MHC class II, was able to both prevent and treat PE-like features in mice. We then determined that γ–δ T cells are critical for the development of PE-like features in mice since γ–δ T-cell knockout mice, like CLIP deficient mice, are resistant to developing PE-like features. Placentas from women with PE exhibit significantly increased levels of γ–δ T cells. These preclinical data demonstrate that CLIP expression and activated γ–δ T cells are responsible for the development of immunologic PE-like features and that temporarily antagonizing CLIP and/or γ–δ T cells may be a therapeutic strategy for PE. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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