期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 95, 期 4, 页码 621-629出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0813443
关键词
immune regulator; apoptosis; LPS; inhibitory
资金
- Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Korea [A092258]
- Brain Korea 21 Project
- World Class University (WCU) Program through the NRF - Ministry of Education, Science and Technology [R31-2008-000-10105-0, R31-10105]
- NRF - Ministry of Education, Science and Technology [NRF-2012R1A1A2044088]
PD-1 expressed on activated DCs suppresses T cell activation via decreasing DC survival. 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.
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