Open AccessB7-H4 as a protective shield for pancreatic islet beta cells
Author(s) -
Annika C. Sun,
Dawei Ou,
Dan S. Luciani,
Garth L. Warnock
Publication year - 2014
Publication title -
world journal of diabetes
Language(s) - English
Resource type - Journals
ISSN - 1948-9358
DOI - 10.4239/wjd.v5.i6.739
Subject(s) - islet , medicine , type 1 diabetes , transplantation , pancreatic islets , beta cell , autoimmunity , immune system , immunology , diabetes mellitus , t cell , downregulation and upregulation , cancer research , endocrinology , biology , biochemistry , gene
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.