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Publication : IL-10 Producing B Cells Protect against LPS-Induced Murine Preterm Birth by Promoting PD1- and ICOS-Expressing T Cells.

First Author  Busse M Year  2022
Journal  Cells Volume  11
Issue  17 PubMed ID  36078100
Mgi Jnum  J:336690 Mgi Id  MGI:7339524
Doi  10.3390/cells11172690 Citation  Busse M, et al. (2022) IL-10 Producing B Cells Protect against LPS-Induced Murine Preterm Birth by Promoting PD1- and ICOS-Expressing T Cells. Cells 11(17)
abstractText  B cells and in particular IL-10-secreting B cells emerge as important players in immune balance during pregnancy. We have recently revealed that CD19-deficient (CD19(-/-)), B cell-specific IL-10-deficient (BIL-10(-/-)) and B cell-deficient microMT pregnant mice are highly susceptible to LPS-induced preterm birth (PTB). We aimed to analyze the ability of IL-10-secreting cells to protect from PTB and the underlying mechanisms. Wild type (WT), CD19(-/-), BIL-10(-/-) and microMT mice were treated with LPS at gd16 and the cellular immune response was investigated 24 h later. LPS-treated BIL-10(-/-) dams showed a more pronounced PTB phenotype compared to WT, CD19(-/-) and microMT females, and increased inflammatory and reduced anti-inflammatory mediator concentrations in the peritoneal cavity and serum. CD19(-/-), BIL-10(-/-) and microMT mice displayed altered immune cell population frequencies in the blood and uterus with lower numbers of IL-10-secreting B cells and T cells. BIL-10(-/-) mothers presented decreased frequencies of uterine CD4+CD25+Foxp3+ Treg cells. Co-stimulatory molecules are critical for feto-maternal tolerance and IL-10 secretion. We found dysregulated PD-1 expression in peripheral blood and ICOS expression in the uterus of CD19(-/-), BIL-10(-/-) and microMT dams. Our data show that B cell-specific IL-10-signaling is essential for a balanced maternal immune response to an inflammatory stimulant that cannot be hampered without IL-10-secreting B cells.
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