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

Table 1 Evidence for immune regulatory and β-cell autonomous roles of B7-H4 in experimental/human diabetes

Role	Model	Summary of findings	Application	Ref.
Autoimmune modulator	NOD mouse	B7-H4 Ig inhibits development of, and reverses newly-onset autoimmune diabetes	Prevents/	[31,33]
			reverses T1D
Allograft protection	NIT cell line	B7-H4 transfected NIT cells promote β-cell allograft survival	Suppresses islet graft rejection	[44]
	Mouse	Adenoviral-transduced B7-H4 donor islets enhanced islet allograft survival, and promotes donor-specific tolerance		[43,46]
	Mouse	B7-H4 transgenic islets improve islet allograft survival	Preserves β-cell mass in T1D/T2D	[51]
Non-immune dependent UPR and cell survival	Pancreatic carcinoma-derived cell lines	B7-H4 knock-down increases cell apoptosis		[56]
regulator	Renal carcinoma tissues and cancer cell lines	Human intracellular B7-H4 is identified as a cytoplasmic-nuclear shuttling protein that contains a NLS		[57]
	Mouse	B7-H4 modulates UPR in isolated pancreatic β-cells		Unpublished
Biomarkers of β-cell immunity	Mouse	B7-H4 RSS0.2 mRNA splice form is correlated with different stages of T1D	Detects β-cell autoimmunity	Unpublished
	Human	Reduced B7-H4 expression and B7-H4/insulin colocalization is detected in pancreata of T1D patients		[25]
	Human	Elevated sB7-H4 is present in RA and newly-onset T1D patients		[61,62]

T1D: Type 1 diabetes; NOD: Non-obese diabetic; UPR: Unfolded protein response; NLS: Nuclear localization signal.