title: 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.
authors.affiliation: National Creative Research Laboratory for Ca Signaling Network and Departments of Biochemistry.
authors.forename: Byung-Ju
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: National Creative Research Laboratory for Ca Signaling Network and Departments of Biochemistry.
authors.forename: Yun-Min
authors.initials: YM
authors.lastname: Choi
authors.affiliation: National Creative Research Laboratory for Ca Signaling Network and Departments of Biochemistry.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Rah
authors.affiliation: National Creative Research Laboratory for Ca Signaling Network and Departments of Biochemistry.
authors.forename: Dae-Ryoung
authors.initials: DR
authors.lastname: Park
authors.affiliation: National Creative Research Laboratory for Ca Signaling Network and.
authors.forename: Seon-Ah
authors.initials: SA
authors.lastname: Park
authors.affiliation: National Creative Research Laboratory for Ca Signaling Network and.
authors.forename: Yun-Jo
authors.initials: YJ
authors.lastname: Chung
authors.affiliation: Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan, 570-752, Korea; and.
authors.forename: Seung-Moon
authors.initials: SM
authors.lastname: Park
authors.affiliation: Urology, and.
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
authors.affiliation: Pathology, Chonbuk National University Medical School, Jeonju, 561-180, Korea;
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.affiliation: National Creative Research Laboratory for Ca Signaling Network and Departments of Biochemistry, Institute of Cardiovascular Research, Chonbuk National University, Jeonju, 561-180, Korea uhkim@chonbuk.ac.kr.
authors.forename: Uh-Hyun
authors.initials: UH
authors.lastname: Kim
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D012661:Semen / Q000276:immunology*
chemical_list: D051997:ADP-ribosyl Cyclase 1
keywords: CD38; dendritic cells; fetomaternal tolerance; regulatory T cells; seminal plasma