Depletion of MHC class II invariant chain peptide or - T-cells ameliorates experimental preeclampsia. uri icon

abstract

  • 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.

published proceedings

  • Clin Sci (Lond)

altmetric score

  • 9

author list (cited authors)

  • Chatterjee, P., Chiasson, V. L., Seerangan, G., De Guzman, E., Milad, M., Bounds, K. R., ... Mitchell, B. M.

citation count

  • 15

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

publication date

  • August 2017