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

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 µMT pregnant mice are highly susceptible to LPSinduced 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 µMT 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 µMT
females, and increased inflammatory and reduced anti-inflammatory mediator concentrations in
the peritoneal cavity and serum. CD19−/−, BIL-10−/− and µMT 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 µMT 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.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88486
Date06 December 2023
CreatorsBusse, Mandy, Zenclussen, Ana Claudia
PublisherMDPI
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation2073-4409, 10.3390/cells11172690

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