Abstract
For the normal development of pregnancy, a balance between immune tolerance and defense is crucial. However, the mechanisms mediating such a balance are not fully understood. CD83 is a transmembrane protein whose expression has been linked to anti-inflammatory functions of T and B cells. The soluble form of CD83, released by cleavage of the membrane-bound protein, has strong anti-inflammatory properties and was successfully tested in different mouse models. It is assumed that this molecule contributes to the establishment of immune tolerance. Therefore, we postulated that the expression of CD83 is crucial for immune tolerance during pregnancy in mice. Here, we demonstrated that the membrane-bound form of CD83 was upregulated in T and B cells during allogeneic murine pregnancies. An upregulation was also evident in the main splenic B cell subtypes: marginal zone, follicular zone, and transitional B cells. We also showed that there was an augmentation in the number of CD83+ cells toward the end of pregnancy within splenic B and CD4+ T cells, while CD83+ dendritic cells were reduced in spleen and inguinal lymph nodes of pregnant mice. Additionally, B lymphocytes in late-pregnancy presented a markedly higher sensitivity to LPS in terms of CD83 expression and sCD83 release. Progesterone induced a dosis-dependent upregulation of CD83 on T cells. Our data suggest that the regulation of CD83 expression represents a novel pathway of fetal tolerance and protection against inflammatory threats during pregnancy.
Highlights
Pregnancy is associated with several immune adaptations that allow the growth of a healthy semiallogeneic fetus
We evaluated the presence of CD83 on CD11c+ and DCIR2+ dendritic cells, CD4+ T cells, and different B-cell populations (Figure 1A)
We found an upregulation of CD83 on B cells and on CD4+ T cells at day 14 of pregnancy (1.76- and 3.18-fold increase, respectively, Figures 1B,C)
Summary
Pregnancy is associated with several immune adaptations that allow the growth of a healthy semiallogeneic fetus. These include a finely regulated shift from a Th1 and Th17 toward a Th2 tolerogenic response driven by anti-inflammatory molecules secreted by, among others, the “so-called” regulatory cells [1]. Several cell types have been described with regulatory functions during pregnancy, including T [2] and B lymphocytes [3]. Lymphocytes with regulatory properties allow the eradication of external threats and limit proinflammatory responses. The presence of regulatory cells at the maternal–fetal interface is crucial in mammals with invasive placentation [4]. A potential dysregulation of regulatory cells may have several consequences on the human health and has been
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