Transforming Growth Factor Beta Signaling in Dendritic Cells Is Required for Immunotolerance to Sperm in the Epididymis
Midura-Kiela, Monica T.
Fleming, Sherry D.
Schultz, Bruce D.
Kiela, Pawel R.
AffiliationUniv Arizona, Dept Pediat
Univ Arizona, Dept Immunobiol
MetadataShow full item record
PublisherFRONTIERS MEDIA SA
CitationPierucci-Alves F, Midura-Kiela MT, Fleming SD, Schultz BD and Kiela PR (2018) Transforming Growth Factor Beta Signaling in Dendritic Cells Is Required for Immunotolerance to Sperm in the Epididymis. Front. Immunol. 9:1882. doi: 10.3389/fimmu.2018.01882
JournalFRONTIERS IN IMMUNOLOGY
Rights© 2018 Pierucci-Alves, Midura-Kiela, Fleming, Schultz and Kiela. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractThe epididymis exhibits a less restrictive physical blood-tissue barrier than the testis and, while numerous immunosuppressive factors have been identified in the latter, no mechanisms for epididymal immunotolerance have been identified to date. Therefore, data are currently insufficient to explain how the immune system tolerates the extremely large load of novel antigens expressed on sperm, which become present in the male body after puberty, i.e., long after central tolerance was established. This study tested the hypothesis that transforming growth factor beta (TGF beta) signaling in dendritic cells (DCs) is required for immunotolerance to sperm located in the epididymis, and that male mice lacking TGF beta signaling in DCs would develop severe epididymal inflammation. To test this, we employed adult Tgfbr2(Delta DC) males, which exhibit a significant reduction of Tgfbr2 expression and TGF beta signaling in DCs, as reported previously. Results show that Tgfbr2(Delta DC) males exhibit sperm-specific immune response and severe epididymal leukocytosis. This phenotype is consistent with epididymal loss of immunotolerance to sperm and suggests that TGF beta signaling in DCs is a factor required for a non-inflammatory steady state in the epididymis, and therefore for male tract homeostasis and function.
NoteOpen access journal.
VersionFinal published version
SponsorsNIH/NIGMS [P20 GM103418]; K-State Johnson Cancer Research Center; K-State College of Veterinary Medicine; NIH [5R01 DK109711]