PD-1 on immature and PD-1 ligands on migratory human langerhans cells regulate antigen-presenting cell activity

Victor Pẽa-Cruz, Sean M. McDonough, Felipe Diaz-Griffero, Christopher P. Crum, Ruben D. Carrasco, Gordon J. Freeman

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Langerhans cells (LCs) are known as sentinels of the immune system that function as professional antigen-presenting cells (APCs) after migration to draining lymph node. LCs are proposed to have a role in tolerance and the resolution of cutaneous immune responses. The Programmed Death-1 (PD-1) receptor and its ligands, PD-L1 and PD-L2, are a co-inhibitory pathway that contributes to the negative regulation of T-lymphocyte activation and peripheral tolerance. Surprisingly, we found PD-1 to be expressed on immature LCs (iLCs) in situ. PD-1 engagement on iLCs reduced IL-6 and macrophage inflammatory protein (MIP)-1α cytokine production in response to TLR2 signals but had no effect on LC maturation. PD-L1 and PD-L2 were expressed at very low levels on iLCs. Maturation of LCs upon migration from epidermis led to loss of PD-l expression and gain of high expression of PD-L1 and PD-L2 as well as co-stimulatory molecules. Blockade of PD-L1 and/or PD-L2 on migratory LCs (mLCs) and DDCs enhanced T-cell activation, as has been reported for other APCs. Thus the PD-1 pathway is active in iLCs and inhibits iLC activities, but expression of receptor and ligands reverses upon maturation and PD-L1 and PD-L2 on mLC function to inhibit T-cell responses.

Original languageEnglish (US)
Pages (from-to)2222-2230
Number of pages9
JournalJournal of Investigative Dermatology
Volume130
Issue number9
DOIs
StatePublished - Sep 1 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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