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- W4308409820 abstract "Abstract Background IL-10 knockout (KO) mice can be protected against experimental autoimmune encephalomyelitis (EAE) with low-dose estrogen (E2) treatment similar to wild type (WT) mice, indicating that IL-10 is not required for E2-induced EAE protection. Our previous study demonstrated that E2 treatment induced an increase in programmed death ligands 1 (PD-L1) and 2 (PD-L2) on monocytes and macrophages in the periphery and within the CNS. In this study, we selectively inhibited the function of PD-L1 and PD-L2 to evaluate their critical role in maintaining E2-induced protection against EAE in IL-10-KO mice. Methods This study used female IL-10 KO mice pre-treated with either E2 or sham pellets seven days prior to induction of EAE and subsequently treated with Vehicle or antibodies to PD-L1, PD-L2 or respective isotype controls. Mice were scored daily for EAE severity over 21 days post-immunization for EAE induction. Cells from the spleen and brain were evaluated by flow cytometry. Results Differences in EAE severity were assessed in E2 and sham pre-treated IL-10-KO mice treated with α-PD-L1 or α-PD-L2 antibodies over the course of disease compared to treatment with Vehicle or anti-isotype antibodies. The results revealed real-time development of severe EAE in E2-pre-treated IL-10-KO mice treated with α-PD-L1 but not α-PD-L2 antibodies, mediated in part by increased percentages of activated CD74 + CD11b + myeloid cells in spleen and brain as well as splenic B-cells, T-cells and CD73 + cells. Conclusion These results demonstrate unequivocally that PD-L1 but not PD-L2 was required to retain the inhibitory effects of E2 on clinical EAE scores in female IL-10-KO mice and further implicate the emergence of the MIF/CD74 axis as a contributing pathogenic mechanism." @default.
- W4308409820 created "2022-11-11" @default.
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- W4308409820 date "2022-11-07" @default.
- W4308409820 modified "2023-09-27" @default.
- W4308409820 title "PD-L1 is Required for Estrogen-induced Protection Against Severe EAE in IL-10 Deficient Mice" @default.
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- W4308409820 doi "https://doi.org/10.21203/rs.3.rs-2188228/v1" @default.
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