TY - JOUR
T1 - PD-1 on immature and PD-1 ligands on migratory human langerhans cells regulate antigen-presenting cell activity
AU - Pẽa-Cruz, Victor
AU - McDonough, Sean M.
AU - Diaz-Griffero, Felipe
AU - Crum, Christopher P.
AU - Carrasco, Ruben D.
AU - Freeman, Gordon J.
N1 - Funding Information:
We thank Dr Branch D. Moody for providing us with the Pam3Cys. This work was supported by NIH grants A108080192, A1056299, and BAA-05-11.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2010.127
DO - 10.1038/jid.2010.127
M3 - Article
C2 - 20445553
AN - SCOPUS:77955710639
SN - 0022-202X
VL - 130
SP - 2222
EP - 2230
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -