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Seminal CD38 is a pivotal regulator for fetomaternal tolerance.


ABSTRACT: A successful pregnancy depends on a complex process that establishes fetomaternal tolerance. Seminal plasma is known to induce maternal immune tolerance to paternal alloantigens, but the seminal factors that regulate maternal immunity have yet to be characterized. Here, we show that a soluble form of CD38 (sCD38) released from seminal vesicles to the seminal plasma plays a crucial role in inducing tolerogenic dendritic cells and CD4(+) forkhead box P3(+) (Foxp3(+)) regulatory T cells (Tregs), thereby enhancing maternal immune tolerance and protecting the semiallogeneic fetus from resorption. The abortion rate in BALB/c females mated with C57BL/6 Cd38(-/-) males was high compared with that in females mated with Cd38(+/+) males, and this was associated with a reduced proportion of Tregs within the CD4(+) T-cell pool. Direct intravaginal injection of sCD38 to CBA/J pregnant mice at preimplantation increased Tregs and pregnancy rates in mice under abortive sonic stress from 48 h after mating until euthanasia. Thus, sCD38 released from seminal vesicles to the seminal plasma acts as an immunoregulatory factor to protect semiallogeneic fetuses from maternal immune responses.

SUBMITTER: Kim BJ 

PROVIDER: S-EPMC4321276 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Seminal CD38 is a pivotal regulator for fetomaternal tolerance.

Kim Byung-Ju BJ   Choi Yun-Min YM   Rah So-Young SY   Park Dae-Ryoung DR   Park Seon-Ah SA   Chung Yun-Jo YJ   Park Seung-Moon SM   Park Jong Kwan JK   Jang Kyu Yun KY   Kim Uh-Hyun UH  

Proceedings of the National Academy of Sciences of the United States of America 20150115 5


A successful pregnancy depends on a complex process that establishes fetomaternal tolerance. Seminal plasma is known to induce maternal immune tolerance to paternal alloantigens, but the seminal factors that regulate maternal immunity have yet to be characterized. Here, we show that a soluble form of CD38 (sCD38) released from seminal vesicles to the seminal plasma plays a crucial role in inducing tolerogenic dendritic cells and CD4(+) forkhead box P3(+) (Foxp3(+)) regulatory T cells (Tregs), th  ...[more]

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