BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth

Autor: Jessica R. Doll, Maria E. Moreno-Fernandez, Traci E. Stankiewicz, Jennifer L. Wayland, Adrienne Wilburn, Benjamin Weinhaus, Claire A. Chougnet, Daniela Giordano, Monica Cappelletti, Pietro Presicce, Suhas G. Kallapur, Nathan Salomonis, Tamara Tilburgs, Senad Divanovic
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 4, Pp 112352- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112352
Popis: Summary: Clinical evidence points to a function for B cell-activating factor (BAFF) in pregnancy. However, direct roles for BAFF-axis members in pregnancy have not been examined. Here, via utility of genetically modified mice, we report that BAFF promotes inflammatory responsiveness and increases susceptibility to inflammation-induced preterm birth (PTB). In contrast, we show that the closely related A proliferation-inducing ligand (APRIL) decreases inflammatory responsiveness and susceptibility to PTB. Known BAFF-axis receptors serve a redundant function in signaling BAFF/APRIL presence in pregnancy. Treatment with anti-BAFF/APRIL monoclonal antibodies or BAFF/APRIL recombinant proteins is sufficient to manipulate susceptibility to PTB. Notably, macrophages at the maternal-fetal interface produce BAFF, while BAFF and APRIL presence divergently shape macrophage gene expression and inflammatory function. Overall, our findings demonstrate that BAFF and APRIL play divergent inflammatory roles in pregnancy and provide therapeutic targets for mitigating risk of inflammation-induced PTB.
Databáze: Directory of Open Access Journals