Protective effects of Fc-fused PD-L1 on two different animal models of colitis
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SCOPUS
- Title
- Protective effects of Fc-fused PD-L1 on two different animal models of colitis
- Authors
- Song, MY; Hong, CP; Park, SJ; Kim, JH; Yang, BG; Park, Y; Kim, SW; Kim, KS; Lee, JY; Lee, SW; Jang, MH; Sung, YC
- Date Issued
- 2015-02
- Publisher
- BMJ
- Abstract
- Objective Programmed death-ligand 1 (PD-L1) has been shown to negatively regulate immune responses via its interaction with PD-1 receptor. In this study, we investigated the effects of PD-L1-Fc treatment on intestinal inflammation using two murine models of inflammatory colitis induced by dextran sulfate sodium (DSS) and T-cell transfer. Design The anti-colitis effect of adenovirus expressing Fc-conjugated PD-L1 (Ad/PD-L1-Fc) and recombinant PD-L1-Fc protein was evaluated in DSS-treated wild-type and Rag-1 knockout (KO) mice. We examined differentiation of T-helper cells, frequency of innate immune cells, and cytokine production by dendritic cells (DCs) in the colon from DSS-treated mice after PD-L1-Fc administration. In Rag-1 KO mice reconstituted with CD4 CD45RB(high) T cells, we assessed the treatment effect of PD-L1-Fc protein on the development of colitis. Results Administration of Ad/PD-L1-Fc significantly ameliorated DSS-induced colitis, which was accompanied by diminished frequency of interleukin (IL)-17A-producing CD4 T cells and increased interferon-gamma-producing CD4 T cells in the colon of DSS-fed mice. The anti-colitic effect of PD-L1-Fc treatment was also observed in DSS-treated Rag-1 KO mice, indicating lymphoid cell independency. PD-L1-Fc modulated cytokine production by colonic DCs and the effect was dependent on PD-1 expression. Furthermore, PD-L1-Fc protein could significantly reduce the severity of colitis in CD4 CD45RB(high) T-cell-transferred Rag-1 KO mice. Conclusions Based on the protective effect of PD-L1-Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1-mediated inhibitory signals have a crucial role in limiting the development of colonic inflammation. This implicates that PD-L1-Fc may provide a novel therapeutic approach to treat inflammatory bowel disease.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/27282
- DOI
- 10.1136/GUTJNL-2014-307311
- ISSN
- 0017-5749
- Article Type
- Article
- Citation
- GUT, vol. 64, no. 2, page. 260 - 271, 2015-02
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