MHC class II invariant chain peptide or gamma-delta T cell depletion ameliorates experimental preeclampsia

Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia; however, the molecular mechanisms involved are unknown.  We tested the hypothesis that Toll-like receptor activation induces MHC class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause preeclampsia-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 preeclampsia-like features in mice.  We then determined that gamma-delta T cells are critical for the development of preeclampsia-like features in mice since gamma-delta T cell knockout mice, like CLIP deficient mice, are resistant to developing preeclampsia-like features.  Placentas from women with preeclampsia exhibit significantly increased levels of gamma-delta T cells.  These preclinical data demonstrate that CLIP expression and activated gamma-delta T cells are responsible for the development of immunologic preeclampsia-like features and that temporarily antagonizing CLIP and/or gamma-delta T cells may be a therapeutic strategy for preeclampsia.

Source: Clinical Science - June 22, 2017 Category: Biomedical Science Authors: Chatterjee, P., Chiasson, V. L., Seerangan, G., De Guzman, E., Milad, M., Bounds, K. R., Gasheva, O., Tobin, R. P., Hatahet, M., Kopriva, S., Jones, K. A., Newell-Rogers, M. K., Mitchell, B. Tags: PublishAheadOfPrint Source Type: research