Protective effects of Fc-fused PD-L1 on two different animal models of colitis

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Title
Protective effects of Fc-fused PD-L1 on two different animal models of colitis
Author(s)
Song, M.Y.; Chun-Pyo Hong; Park, S.J.; Jung-Hwan Kim; Bo-Gie Yang; Park, Y.; Kim, S.W.; Kwang Soon Kim; Lee, J.Y.; Lee, S.W.; Myoung Ho Jang; Sung, Y.C.
Publication Date
2015-01
Journal
GUT, v.64, no.2, pp.260 - 271
Publisher
B M J PUBLISHING GROUP
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 CD45RBhigh 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)-17Aproducing CD4 T cells and increased interferon-γ- 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 CD45RBhigh 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://pr.ibs.re.kr/handle/8788114/745
ISSN
0017-5749
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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