Murine abortion is associated with enhanced interleukin-6 levels at the feto-maternal interface

Zenclussen, Ana Claudia; Blois, Sandra M.; Stumpo, Rita; Olmos, Sofı́a; Arias, Karina; Borel, Ileana Malán; Roux, M; Margni, Ricardo A.

doi:10.1016/j.cyto.2003.08.002

Cited by 78 publications

(72 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we concentrated on the mechanisms by which pregnancy-induced Treg generate tolerance and enable fetal survival in a well-established model of murine abortion, namely the CBA/J Â DBA/2J abortion-prone combination [17]. From our recent study, we know that Treg may be antigen-specific during pregnancy (at least in our murine model), since the transfer of Treg from BALB/c (H2 d )-pregnant CBA/J (H2 k ) females could prevent fetal rejection while the transfer from Treg obtained from virgin naive CBA/J females could not [28].…”

Section: Discussionmentioning

confidence: 99%

“…The "Th1/Th2 paradigm" proposes that Th2-type cytokines such as IL-4 and IL-10 may favor the maintenance of mammalian pregnancy [6,[10][11][12], whereas the excessive production of Th1 cytokines (IL-2, IFN-c, TNF-a) would mediate the rejection of the fetus at the feto-maternal interface [10,[13][14][15][16][17]. Thus, we wondered whether the protective effects observed after transfer of pregnancy-induced Treg were related to a down-regulation of "abortive" cytokines (Th1) and/or to an up-regulation of pregnancy-protective (Th2) cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…As already confirmed in several studies, the mating combination CBA/J Â DBA/2J represents the abortion-prone group [17,63]. Two-month-old CBA/J females were paired with 2-4-month-old DBA/2J or BALB/c males, checked twice a day for vaginal plugs and separated from the males if mated.…”

Section: Animals and Pregnancy Outcomementioning

confidence: 95%

“…The abortion (resorption) sites could be identified by their small size accompanied by a necrotic, hemorrhagic appearance, compared with normal embryos and placentas. The percentage of abortion was calculated as the ratio of resorption sites and total implantation sites (resorption plus normal implantation sites) as described previously [17].…”

Section: Animals and Pregnancy Outcomementioning

confidence: 99%

“…Th1/Th2 cytokine balance with Th2 predominance has been seen as a very important mechanism determining the survival of the fetus in the maternal uterus [6][7][8][9][10][11][12][13][14][15][16][17]. However, mice genetically deficient for IL-4 and IL-10 do not show disturbed pregnancy [18], suggesting that Th2 cells are not essential for normal pregnancy and alloreactive Th1 cells must be differently regulated, as already proposed [19][20][21].…”

Section: Introductionmentioning

confidence: 97%

See 4 more Smart Citations

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

et al. 2005

View full text Add to dashboard Cite

The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN-c and TNF-a were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-b and heme oxygenase-1 at the fetal-maternal interface were dramatically up-regulated after Treg transfer, while the levels of indolamine 2,3-dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Animals and Pregnancy Outcomementioning

confidence: 95%

Section: Animals and Pregnancy Outcomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 3 more Smart Citations

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

et al. 2005

View full text Add to dashboard Cite

show abstract

Diminished miR-374c-5p negatively regulates IL (interleukin)-6 in unexplained recurrent spontaneous abortion

Zhao

Hei

et al. 2022

J Mol Med

View full text Add to dashboard Cite

Regulatory T cells in pregnancy

Zenclussen

2006

Springer Semin Immun

View full text Add to dashboard Cite

Tolerance mechanisms are responsible for the survival of the fetus within the maternal uterus without being attacked by the cells of the maternal immune system despite their direct contact. Regulatory T cells (Treg) were claimed to be important players in the tolerance towards the fetus bearing alloantigens. Recent evidence confirmed an augmentation in the number of Treg during pregnancy and, most importantly, diminished numbers of Treg were associated with immunological rejection of the fetus. This could be prevented by adoptively transferring CD4(+)/CD25(+) Treg cells from normal pregnant mice into abortion-prone animals. Treg prevented abortion while creating a transient tolerant microenvironment characterized by high levels of TGF-beta, LIF, and HO-1. Downregulated levels of Treg were accordingly also reported during human miscarriage. Furthermore, we have evidence suggesting that, to be protective, Treg need to be activated by male antigens during pregnancy.

show abstract

Murine abortion is associated with enhanced interleukin-6 levels at the feto-maternal interface

Cited by 78 publications

References 44 publications

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

Diminished miR-374c-5p negatively regulates IL (interleukin)-6 in unexplained recurrent spontaneous abortion

Regulatory T cells in pregnancy

Contact Info

Product

Resources

About