title: TNF-α and TGF-β 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-α expression. Exogenous TNF-α restored PD-L1 expression on lupus monocytes. Conversely, TGF-β 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-α and TGF-β. 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.
authors.affiliation: Seattle Children’s Research Institute. University of Washington, Seattle, WA, USA.
authors.forename: Jing-Ni
authors.initials: JN
authors.lastname: Ou
authors.forename: Alice E
authors.initials: AE
authors.lastname: Wiedeman
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stevens
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000503:physiopathology*; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha