IL-1R1 blockade attenuates liver injury through inhibiting the recruitment of myeloid-derived suppressor cells in sepsis.
IL-1R1 blockade attenuates liver injury through inhibiting the recruitment of myeloid-derived suppressor cells in sepsis.
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DOI：
10.1016/j.bbrc.2022.06.038
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发表时间：
2022-06
影响因子：
3.1
通讯作者：
Minjie Luo;Hao Wang-;Ke Liu;Mei-dong Liu;Sipin Tan;Yaxi Zhu;Huali Zhang
中科院分区：
文献类型：
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作者：
Minjie Luo;Hao Wang-;Ke Liu;Mei-dong Liu;Sipin Tan;Yaxi Zhu;Huali Zhang
髓源性抑制细胞（MDSCs）可从骨髓向外周组织或免疫器官迁移，这与脓毒症的预后不良有关。MDSCs的干预可能是有效治疗脓毒症的潜在靶点。在本研究中，我们证明了用重组人IL-1R拮抗剂Anakinra阻断IL-1R1或IL-1R1缺乏对脓毒症小鼠的肝损伤有保护作用。可能的机制是Anakinra治疗和IL-1R1敲除抑制了脓毒症中MDSCs向肝脏的迁移，从而减轻了MDSCs对以CD4+和CD8+T细胞比例下降为特征的效应T细胞的免疫抑制。此外，Anakinra和IL-1R1缺乏明显增强了脓毒症小鼠肝脏中由促炎M1型巨噬细胞向抗炎M2型巨噬细胞的转换和细菌清除能力，从而减轻了肝损伤。综上所述，这些发现为揭示IL-1R1与MDSCs在脓毒症中的关系提供了新的思路，从而为改善脓毒症肝损伤提供了潜在的有效靶点。
Myeloid-derived suppressor cells (MDSCs) mobilize and migrate from bone marrow to peripheral tissues or immune organs, which is associated with poor prognosis in sepsis. Intervention of MDSCs might be a potential target for the effective treatment of sepsis. In the present study, we demonstrated that IL-1R1 blockade with either recombinant human IL-1R antagonist Anakinra or IL-1R1 deficiency had a protective effect on the liver injury in septic mice. The possible mechanism was that Anakinra treatment and IL-1R1 knockout inhibited the migration of MDSCs to the liver in sepsis, thus attenuating the immune suppression of MDSCs on effector T cells characterized with the decrease in proportion of CD4+and CD8+T cells. Furthermore, the switch from pro-inflammatory M1 macrophage to anti-inflammatory M2 phenotype and the ability of bacterial clearance in the liver of septic mice were enhanced obviously by Anakinra and IL-1R1 deficiency, which contributes to the attenuated liver injury. Taken together, these findings provide new ideas for revealing the relationship between IL-1R1 and MDSCs in sepsis, thereby providing a potentially effective target for ameliorating septic liver injury.