Grim-19 deficiency promotes decidual macrophage autophagy in recurrent spontaneous abortion

Grim-19 deficiency promotes decidual macrophage autophagy in recurrent spontaneous abortion

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Dysregulation of decidual macrophages leads to the occurrence of recurrent spontaneous abortion (RSA).However, the role Beyond the Score: Timbre Analysis in Avant-garde Music of macrophages in RSA occurrence remains unclear.In this study, we found that the expression of Grim-19 was decreased, and the expression of autophagy related proteins Beclin1, LC3B II/I and BNIP3 was markedly upregulated in decidual macrophages of RSA patients compared with the normal pregnancy group.Furthermore, we demonstrated that downregulation of GRIM-19 increased the expression of autophagy related proteins Beclin1, LC3B II/I, BNIP3 and the proinflammatory cytokines IL1B, IL6 and TNFa in uterine mononuclear cells of GRIM-19+/- mice.

The proportion of CD45+CD11b+F4/80+LC3B+ cells in GRIM-19+/- mouse uteri was significantly higher than that in WT mouse uteri.In addition, we confirmed that inhibition of Grim-19 by Audit result and its users siRNA enhanced the expression of autophagy related proteins in RAW264.7 cells and THP-1 cells.More importantly, downregulation of Grim-19 in RAW264.

7 cells promoted the release of proinflammatory cytokines and promoted phagocytic activity, which could be reversed by autophagy blockade.For THP-1-derived macrophages, the results of RNA-seq suggested that Grim-19 mainly modulates immune and inflammatory-related pathways, leading to cytokine production, and thus contributing to inflammation.Therefore, our data reveal that Grim-19 deficiency influences macrophage function, characterized by enhanced proinflammatory cytokines and phagocytic activity, and this might be regulated by autophagy.This may represent a novel mechanism for the occurrence of RSA.