Plasma Transfusion Promoted Reprogramming CD4+ T Lymphocytes Immune Response in Severe Sepsis Mice Model Through Modulating the Exosome Protein Galectin 9

血浆输注通过调节外泌体蛋白 Galectin 9 促进严重脓毒症小鼠模型中重编程 CD4+ T 淋巴细胞免疫反应

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作者:Lei Zhang, Jian-Ping Zhang, Yang Liu, Huan Wang, Yong Cheng, Jin-Huo Wang, Wen-Jie Zhang, Zhen-Zhou Li, Jian-Rong Guo

Abstract

Sepsis is a life-threatening disease that results in excessive stimulation of the host's immune cells. In the animal study, the purpose was to investigate the roles of fresh frozen plasma (FFP) transfusion in shaping the CD4+ T lymphocytes immune response through modulating the secreted exosome protein Galectin-9 in mice with severe sepsis. By using Western blot analysis, we first identified that the protein Galectin-9 is highly accumulated in the blood plasma of severe sepsis mice, and with transmission electron microscopy (TEM) and protein analysis, we found that Galectin-9 is a secreted exosome protein. Thereafter, we treated the severe sepsis mice with the antibiotic Cefuroxime Axetil; one group of mice received FFP transfusion and the other group of mice received normal saline. Surprisingly, the FFP transfusion reduced the secretion of exosome protein Galectin-9 and there was crosstalking between the exosome protein Galectin-9 and CD4+ T lymphocytes in mice with severe sepsis. Results showed that the proliferation of T helper (Th) cells (Th1 and Th17) was promoted, and regulatory T (Treg) cells' maintenance was inhibited in the sepsis mice after receiving FFP transfusion. Correspondingly, this immune reprogrammed activity shaped the inflammatory cytokine secretion with an increase in the interleukin (IL)-1β, IL-6, and interferon-gamma levels, while it decreased IL-10 levels. Taken together, it was suggested that FFP transfusion promoted reprogramming of CD4+ T lymphocytes' immune response through inhibiting the secretion of exosome protein Galectin-9 in mice with severe sepsis to relieve immunosuppression.

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