@article {542381,
	title = {Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice.},
	journal = {J Immunol},
	volume = {181},
	number = {4},
	year = {2008},
	month = {2008 Aug 15},
	pages = {2513-21},
	abstract = {MRL/MpJ-Fas(lpr) (MRL-Fas(lpr)) mice develop a spontaneous T cell and macrophage-dependent autoimmune disease that shares features with human lupus. Interactions via the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway down-regulate immune responses and provide a negative regulatory checkpoint in mediating tolerance and autoimmune disease. Therefore, we tested the hypothesis that the PD-1/PD-L1 pathway suppresses lupus nephritis and the systemic illness in MRL-Fas(lpr) mice. For this purpose, we compared kidney and systemic illness (lymph nodes, spleen, skin, lung, glands) in PD-L1 null (-/-) and PD-L1 intact (wild type, WT) MRL-Fas(lpr) mice. Unexpectedly, PD-L1(-/-);MRL-Fas(lpr) mice died as a result of autoimmune myocarditis and pneumonitis before developing renal disease or the systemic illness. Dense infiltrates, consisting of macrophage and T cells (CD8(+) > CD4(+)), were prominent throughout the heart (atria and ventricles) and localized specifically around vessels in the lung. In addition, once disease was evident, we detected heart specific autoantibodies in PD-L1(-/-);MRL-Fas(lpr) mice. This unique phenotype is dependent on MRL-specific background genes as PD-L1(-/-);MRL(+/+) mice lacking the Fas(lpr) mutation developed autoimmune myocarditis and pneumonitis. Notably, the transfer of PD-L1(-/-);MRL(+/+) bone marrow cells induced myocarditis and pneumonitis in WT;MRL(+/+) mice, despite a dramatic up-regulation of PD-L1 expression on endothelial cells in the heart and lung of WT;MRL(+/+) mice. Taken together, we suggest that PD-L1 expression is central to autoimmune heart and lung disease in lupus-susceptible (MRL) mice.},
	keywords = {Animals, Antigens, CD274, Antigens, CD80, Antigens, CD95, Antigens, Surface, Apoptosis Regulatory Proteins, Autoimmune Diseases, Bone Marrow Transplantation, Female, Genetic Predisposition to Disease, Immunophenotyping, Lupus Erythematosus, Systemic, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Mice, Knockout, Mice, Transgenic, Myocarditis, Peptides, Pneumonia, Programmed Cell Death 1 Receptor, Radiation Chimera, Signal Transduction},
	issn = {1550-6606},
	author = {Lucas, Julie A and Menke, Julia and Rabacal, Whitney A and Schoen, Frederick J and Sharpe, Arlene H and Kelley, Vicki R}
}
