Endogenous programmed death ligand-1 restrains the development and onset of Sjӧgren's syndrome in non-obese diabetic mice.

Sci Rep

Department of Immunology and Infectious Diseases, the Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.

Published: December 2016

Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sjögren's syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD/ShiLtJ mice repeatedly during a 9-day period. PD-L1 blockade accelerated leukocyte infiltration and caspase-3 activation in the submandibular gland (SMG), production of antinuclear and anti-M3 muscarinic acetylcholine receptor (M3R) autoantibodies and impairment of saliva secretion, indicative of accelerated development and onset of SS. The effect of PD-L1 blockade was associated with increased T- and B cells and T helper 1 cytokine IFN-γ in the SMG. Local administration of exogenous IFN-γ to the SMG led to impaired salivary secretion accompanied by down-regulation of aquaporin 5 and an increase in anti-M3R autoantibodies. Conversely, neutralization of IFN-γ markedly improved salivary secretion and aquaporin 5 expression in anti-PD-L1-treated NOD/ShiLtJ mice. Hence, endogenous PD-L1 hinders the development and onset of SS in NOD mice, in part by suppressing IFN-γ production.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155421PMC
http://dx.doi.org/10.1038/srep39105DOI Listing

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