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Review
. 2014 Dec 15;5(6):739-46.
doi: 10.4239/wjd.v5.i6.739.

B7-H4 as a protective shield for pancreatic islet beta cells

Annika C Sun  1 , Dawei Ou  1 , Dan S Luciani  1 , Garth L Warnock  1
Affiliations
Review

B7-H4 as a protective shield for pancreatic islet beta cells

Annika C Sun et al. World J Diabetes. .

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.

Keywords: Autoimmunity; Biomarker; Co-stimulation blockade; Diabetes mellitus; Transplantation.

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