TNF-α and TGF-β counter-regulate PD-L1 expression on monocytes in systemic lupus erythematosus

Sci Rep. 2012;2:295. doi: 10.1038/srep00295. Epub 2012 Mar 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • B7-H1 Antigen / physiology*
  • Humans
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / physiopathology*
  • Monocytes / metabolism*
  • RNA, Messenger / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha