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BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth

ABSTRACT: Emerging clinical evidence points to a function for B cell activating factor (BAFF) in pregnancy. However, a direct role for BAFF-axis members including BAFF, the closely related a proliferation-inducing ligand (APRIL), and their respective receptors in pregnancy has not been examined. This study demonstrates that loss of BAFF results in decreased inflammatory responsiveness and decreased susceptibility to inflammation-induced preterm birth (PTB). In contrast, loss of APRIL increases inflammatory responsiveness and susceptibility to PTB. Consistent with overlapping receptor utilization by BAFF and APRIL, deletion of BAFF-axis receptors is not sufficient to modify susceptibility to PTB. Critically, therapeutic administration of BAFF/APRIL monoclonal antibodies or recombinant proteins is sufficient to manipulate susceptibility to inflammation-induced PTB. Further, macrophages are identified as the principle BAFF producing immune cells at the maternal-fetal interface and BAFF and APRIL divergently manipulate macrophage gene expression and inflammatory function. Genes linked to labor initiation are upregulated in WT and APRIL deficient macrophages while downregulated in BAFF deficient macrophages and correlate with myeloid gene expression in human placental samples during labor. Thus, BAFF and APRIL play important, but divergent, counterregulatory inflammatory roles in pregnancy and provide new therapeutic targets for mitigating the risk of PTB.

ORGANISM(S): Mus musculus

PROVIDER: GSE202811 | GEO | 2023/08/03

REPOSITORIES: GEO

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