Depletion of MHC class II invariant chain peptide or - T-cells ameliorates experimental preeclampsia.
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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 - T cells are critical for the development of PE-like features in mice since - 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 - T cells. These preclinical data demonstrate that CLIP expression and activated - T cells are responsible for the development of immunologic PE-like features and that temporarily antagonizing CLIP and/or - T cells may be a therapeutic strategy for PE.
author list (cited authors)
Chatterjee, P., Chiasson, V. L., Seerangan, G., De Guzman, E., Milad, M., Bounds, K. R., ... Mitchell, B. M.
complete list of authors
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