A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in Lymphocytes from Pregnant Mice

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.

The CD83 Molecule – An Important Immune Checkpoint

“…Moreover, patients with AR showed significantly reduced sCD83 serum levels, which were inversely correlated with IgE-levels (70). Since B cells are presumably the major source of naturally occurring sCD83 (16,71), these new data perfectly fit the Th2-skewed immunity observed in mice with CD83-deficient B cells (47).…”

“…Apart from this, IDO activity, also likely induced by CD83, has been shown to be essential for fetal tolerance (119,122). In this respect, a striking recent murine study revealed that B and T lymphocytes, but not DCs, upregulate CD83 expression at day 14 of pregnancy (71). Moreover, the sexual hormone progesterone induces CD83 expression in murine T and B cells, but also in DCs in vitro.…”

CD83 orchestrates immunity toward self and non-self in dendritic cells

“…This member of the Ig superfamily is expressed primarily on activated leukocytes, including DCs and regulatory T cells (Tregs), as well as on thymic epithelial cells (TECs) (6)(7)(8)(9). A soluble form of CD83 (sCD83), comprising the extracellular domain, was detected at low levels in sera of healthy individuals and in increased concentrations in patients with hematological malignancies (10)(11)(12), and reports suggested B cells as a major source of naturally occurring sCD83 (13). Several studies demonstrated profound immunomodulatory effects of sCD83 in different animal models of autoimmune diseases and transplantation (14)(15)(16)(17)(18).…”

CD83 is locally regulated and differentially expressed in disturbed murine pregnancy

“…Single-cell suspensions from para-aortic lymph nodes, inguinal lymph nodes, and thymus were obtained as previously described (Packhäuser et al 2017). The tissue was carefully pressed through a 40-µm nylon cell strainer and washed with PBS.…”

“…Recently, we suggested that the soluble form of the transmembrane molecule CD83 (sCD83) could represent an important factor contributing to pregnancy maintenance (Packhäuser et al 2017). Anti-inflammatory properties of sCD83 have been extensively examined in mouse models of autoimmunity, allograft transplantation and inflammatory disease (Lan et al 2010, Bock et al 2013, Starke et al 2013, Eckhardt et al 2014, Lin et al 2018.…”