TNF-α and TGF-β Counter-Regulate PD-L1 Expression on Monocytes in Systemic Lupus Erythematosus
| Autor: | Anne M. Stevens, Jing Ni Ou, Alice E. Wiedeman |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
T cell
Article B7-H1 Antigen Monocytes Transforming Growth Factor beta immune system diseases medicine Humans Lupus Erythematosus Systemic RNA Messenger skin and connective tissue diseases Multidisciplinary Lupus erythematosus Systemic lupus erythematosus biology Tumor Necrosis Factor-alpha business.industry RNA Transforming growth factor beta medicine.disease Peripheral medicine.anatomical_structure Immunology biology.protein Tumor necrosis factor alpha business Transforming growth factor |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep00295 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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