Depletion of MHC class II invariant chain peptide or γ-δ T-cells ameliorates experimental preeclampsia

• Published in: Clinical science (1979) Vol. 131; no. 15; p. 2047
• Main 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
• Format: Journal Article
• Language: English
• Published: England 01-08-2017
• Subjects: Animals; Antigens, Differentiation, B-Lymphocyte - genetics; Antigens, Differentiation, B-Lymphocyte - immunology; Female; Genes, MHC Class II; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Humans; Male; Mice; Mice, Inbred C57BL; Pre-Eclampsia - genetics; Pre-Eclampsia - immunology; Pregnancy; T-Lymphocytes - immunology; Toll-Like Receptors; cytokines; preeclampsia; innate immunity; inflammation; hypertension
• ISSN: 1470-8736
• 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 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.