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Negative role of inducible PD-1 on survival of activated dendritic cells

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Title
Negative role of inducible PD-1 on survival of activated dendritic cells
Author(s)
Seong Jeong Park; Hong Namkoong; Junsang Doh; Jong-Cheol Choi; Bo-Gie Yang; Yunji Park; Young Chul Sung
Publication Date
2014-04
Journal
JOURNAL OF LEUKOCYTE BIOLOGY, v.95, no.4, pp.621 - 629
Publisher
FEDERATION AMER SOC EXP BIOL
Abstract
PD-1 is a well-established negative regulator of T cell responses by inhibiting proliferation and cytokine production of T cells via interaction with its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), expressed on non-T cells. Recently, PD-1 was found to be expressed in innate cells, including activated DCs, and plays roles in suppressing production of inflammatory cytokines. In this study, we demonstrate that PD-1 KO DCs exhibited prolonged longevity compared with WT DCs in the dLNs after transfer of DCs into hind footpads. Interestingly, upon LPS stimulation, WT DCs increased the expression of PD-1 and started to undergo apoptosis. DCs, in spleen of LPS-injected PD-1 KO mice, were more resistant to LPS-mediated apoptosis in vivo than WT controls. Moreover, treatment of blocking anti-PD-1 mAb during DC maturation resulted in enhanced DC survival, suggesting that PD-1: PD-L interactions are involved in DC apoptosis. As a result, PD-1-deficient DCs augmented T cell responses in terms of antigen-specific IFN- production and proliferation of CD4 and CD8 T cells to a greater degree than WT DCs. Moreover, PD-1 KO DCs exhibited increased MAPK1 and CD40–CD40L signaling, suggesting a possible mechanism for enhanced DC survival in the absence of PD-1 expression. Taken together, our findings further extend the function of PD-1, which plays an important role in apoptosis of activated DCs and provides important implications for PD-1-mediated immune regulation. J. Leukoc. Biol. 95: 621–629; 2014.
URI
https://pr.ibs.re.kr/handle/8788114/793
DOI
10.1189/jlb.0813443
ISSN
0741-5400
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > 1. Journal Papers (저널논문)
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