title: B7-H4 as a protective shield for pancreatic islet beta cells.
abstract: Auto- and alloreactive T cells are major culprits that damage β-cells in type 1 diabetes (T1D) and islet transplantation. Current immunosuppressive drugs can alleviate immune-mediated attacks on islets. T cell co-stimulation blockade has shown great promise in autoimmunity and transplantation as it solely targets activated T cells, and therefore avoids toxicity of current immunosuppressive drugs. An attractive approach is offered by the newly-identified negative T cell co-signaling molecule B7-H4 which is expressed in normal human islets, and its expression co-localizes with insulin. A concomitant decrease in B7-H4/insulin co-localization is observed in human type 1 diabetic islets. B7-H4 may play protective roles in the pancreatic islets, preserving their function and survival. In this review we outline the protective effect of B7-H4 in the contexts of T1D, islet cell transplantation, and potentially type 2 diabetes. Current evidence offers encouraging data regarding the role of B7-H4 in reversal of autoimmune diabetes and donor-specific islet allograft tolerance. Additionally, unique expression of B7-H4 may serve as a potential biomarker for the development of T1D. Future studies should continue to focus on the islet-specific effects of B7-H4 with emphasis on mechanistic pathways in order to promote B7-H4 as a potential therapy and cure for T1D.
authors.affiliation: Annika C Sun, Dawei Ou, Dan S Luciani, Garth L Warnock, Department of Surgery, University of British Columbia, Vancouver BC V5Z 4E3, Canada.
authors.forename: Annika C
authors.initials: AC
authors.lastname: Sun
authors.affiliation: Annika C Sun, Dawei Ou, Dan S Luciani, Garth L Warnock, Department of Surgery, University of British Columbia, Vancouver BC V5Z 4E3, Canada.
authors.forename: Dawei
authors.initials: D
authors.lastname: Ou
authors.affiliation: Annika C Sun, Dawei Ou, Dan S Luciani, Garth L Warnock, Department of Surgery, University of British Columbia, Vancouver BC V5Z 4E3, Canada.
authors.forename: Dan S
authors.initials: DS
authors.lastname: Luciani
authors.affiliation: Annika C Sun, Dawei Ou, Dan S Luciani, Garth L Warnock, Department of Surgery, University of British Columbia, Vancouver BC V5Z 4E3, Canada.
authors.forename: Garth L
authors.initials: GL
authors.lastname: Warnock
keywords: Autoimmunity; Biomarker; Co-stimulation blockade; Diabetes mellitus; Transplantation