TITLE:
Macrophage PD-L1 strikes back: PD-1/PD-L1 interaction drives macrophages toward regulatory subsets
AUTHORS:
Yun-Jung Lee, Young-Hye Moon, Kyeong Eun Hyung, Jong-Sun Yoo, Mi Ji Lee, Ik Hee Lee, Byung Sung Go, Kwang Woo Hwang
KEYWORDS:
Regulatory Macrophage; PD-1; PD-L1
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.8C,
August
19,
2013
ABSTRACT: Activated macrophages have been simply de?ned as
cells that secrete in?ammatory mediators and kill intracellular pathogens until
few years ago. Recent studies have proposed a new classification system to
separate activated macrophages based on their functional phenotypes: host
defense, wound healing, and immune regulation. Regulatory macrophages can arise
following innate or adaptive immune responses and hinder macrophage-mediated
host defense and inflammatory functions by inhibiting the production of
pro-inflammatory mediators. In this study, we investigated whether PD-1 and
PD-L1 interaction between macrophages and T cells alters macrophage
activities. Our data provide evidence for PD-1/PD-L1 engagement inducing a regulatory
profile in macrophages. Regulatory macrophages derived from PD-L1 signaling
lost their host defense activity, which consists of the production of
pro-inflammatory cytokine IL-6 and the exhibition of increased IL-10, SPHK1
and LIGHT gene levels in early phases of LPS stimulation. This differentiation
seems to occur through excessive activation of TLR4 downstream MAPK signaling
pathways. Regulatory macrophages induced from PD-1/PD-L1 interaction decrease inflammatory mediators and produce anti-inflammatory cytokines, so this
macrophage subset has been under considerable attention as a possible immune
regulation mechanism. Understanding and modulating regulatory macrophages may
lead to new approches to treat or prevent auto-immune diseases such as type I
diabetes, rheumatic syndrome and hypersensitivity-related diseases, which are
concerned with the overproduction of inflammatory cytokines in macroages.