TNF-? and TGF-? counter-regulate PD-L1 expression on monocytes in systemic lupus erythematosus.

ABSTRACT: Monocytes in patients with systemic lupus erythematosus (SLE) are hyperstimulatory for T lymphocytes. We previously found that the normal program for expression of a negative costimulatory molecule programmed death ligand-1 (PD-L1) is defective in SLE patients with active disease. Here, we investigated the mechanism for PD-L1 dysregulation on lupus monocytes. We found that PD-L1 expression on cultured SLE monocytes correlated with TNF-? expression. Exogenous TNF-? restored PD-L1 expression on lupus monocytes. Conversely, TGF-? inversely correlated with PD-L1 in SLE and suppressed expression of PD-L1 on healthy monocytes. Therefore, PD-L1 expression in monocytes is regulated by opposing actions of TNF-? and TGF-?. As PD-L1 functions to fine tune lymphocyte activation, dysregulation of cytokines resulting in reduced expression could lead to loss of peripheral T cell tolerance.

SUBMITTER: Ou JN 

PROVIDER: S-EPMC3291882 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature