Depletion of MHC class II invariant chain peptide or gamma-delta T-cells ameliorates experimental preeclampsia

作者：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^*

来源：Clinical Science, 2017, 131(15): 2047-2058.

DOI：10.1042/CS20171008

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 gamma-delta T cells are critical for the development of PE-like features in mice since gamma-delta 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 gamma-delta T cells. These preclinical data demonstrate that CLIP expression and activated gamma-delta T cells are responsible for the development of immunologic PE-like features and that temporarily antagonizing CLIP and/or gamma-delta T cells may be a therapeutic strategy for PE.

• 出版日期2017-8-1