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The Immunomodulatory Features of Mesenchymal Stromal Cells Derived from Wharton’s Jelly, Amniotic Membrane, and Chorionic Villi In Vitro and In Vivo Data
Published in Ornella Parolini, Antonietta Silini, Placenta, 2016
Marta Magatti, Mohamed H. Abumaree, Antonietta R. Silini, Rita Anzalone, Salvatore Saieva, Eleonora Russo, Maria Elena Trapani, Giampiero La Rocca, Ornella Parolini
HLA-G is a nonclassical HLA class Ib molecule known to have immune regulatory properties mediated by the interaction with ILT receptors (ILT-2, ILT-3, and ILT-4) (Allan et al. 2000; Hunt et al. 2005). HLA-G displays relevant immune functions through the interaction with these inhibitory receptors, which are expressed by T cells, B cells, NK cells, and mononuclear phagocytes. Indeed, HLA-G modulates cytokine release from human allogeneic PBMCs (Kanai et al. 2001), prevents the proliferation of CD4-T cells, and directs them toward an immunosuppressive phenotype (LeMaoult et al. 2004). In addition, HLA-G induces CD8-T cell apoptosis (Contini et al. 2003; Fournel et al. 2000), or it can even reduce the production of CD8, a major coreceptor/activator cell surface molecule (Contini et al. 2003; Shiroishi et al. 2003). Other reports have shown that HLA-G inhibits NK cell toxicity (Khalil-Daher et al. 1999) and can lead mononuclear phagocytes into suppressive modes characterized by high production of anti-inflammatory cytokines (McIntire et al. 2004). Moreover, HLA-G appears to play a role in the immune tolerance during pregnancy by evading a maternal immune response against the fetus and by inducing the expansion of Treg cells, which would contribute to the suppression of effector responses to alloantigens (Gregori et al. 2015; Petroff 2005).
Reproductive immunomodulatory functions of B cells in pregnancy
Published in International Reviews of Immunology, 2020
Sulagna Dutta, Pallav Sengupta, Nazmul Haque
hCG, a heterodimeric primate-specific glycoprotein in placenta, has four variants, namely hyperglycosylated hCG (hCG-H), total hCG, pituitary hCG and free β-subunit, each secreted by varied cells with distinct functions [120]. After the onset of pregnancy in humans and until the completion of the first trimester, the total hCG level is rapidly increased reaching its peaks between the 9th and 12th week followed by a gradual decline in level until parturition, although remaining greater all through the pregnancy tenure than in a nonpregnant woman [121]. Differentiated syncytiotrophoblasts produce hCG which in turn stimulates corpus luteum to produce P4 [122]. Moreover, trophoblast invasion and thereby implantation is facilitated by hCG [123,124], inducing angiogenesis, and also nourishing the fetus [90,98,125]. It is evident that LH and hCG have a role in immune tolerance during pregnancy rendering fetal endurance to survive [126]. These gonadotropins influence upon immune cells through their specific LH/CG receptor and mannose receptor for hCG. Secretion of hCG is obligatory to maintain corpus luteum E2 and P4 production in pregnancy till the time when the development of placenta is complete and can mimic the role the corpus luteum [127]. In recent years, several unconventional hCG hormone functions have surfaced including its immunomodulatory capacity affecting T cells [128], uterine NK cells [129] and other competent immune cells [90,130].
Application of amniotic membrane in reconstructive urology; the promising biomaterial worth further investigation
Published in Expert Opinion on Biological Therapy, 2019
Jan Adamowicz, Shane Van Breda, Dominik Tyloch, Marta Pokrywczynska, Tomasz Drewa
AM, as all placental tissue, is immune-privileged and shows immunomodulatory properties that regulate immune tolerance in pregnancy. HLA-G (Human Leukocyte Antigen-G) and Fas ligands identified on the surface of AM were recognized as major tolerogenic molecules during pregnancy and critical factors responsible for the immunosuppressive potential of AM. HLA-G can modulate allogeneic immune responses into tolerance and thus prevent extensive migration of inflammatory cells toward AM. Interestingly, mature epithelial cells cultivated on AM were shown to have an increased HLA-G expression on their surface [40]. This remarkable observation indicated that besides modulation of the mature tissue inflammatory response, AM could rearrange their immunological profile.
Fetomaternal Immune Tolerance: Crucial Mechanisms of Tolerance for Successful Pregnancy in Humans
Published in Immunological Investigations, 2022
Yousef Yousefzadeh, Mohammad Sadegh Soltani-Zangbar, Maryam Hemmatzadeh, Navid Shomali, Ata Mahmoodpoor, Javad Ahmadian Heris, Mehdi Yousefi
In addition to the fetomaternal tolerance mechanisms mentioned above, other significant mechanisms have been reported to be involved in this process (Ochtrop 2017). The phosphocholination of polysaccharide moieties in proteins at the post-translational level has been found in both eukaryotes and prokaryotes and plays critical roles in regulating the immune system (Kulshrestha 2018). A broad range of placental proteins has been demonstrated to undergo the phosphocholination process. Such a tissue-specific post-translational modification plays functional roles in fetomaternal immune tolerance during pregnancy (Lovell et al. 2007). Some essential proteins, which are phosphocholinated in the placenta, include the precursors of corticotropin-releasing hormone, adrenocorticotropin, activin, hemokinin, placental neurokinin B, and follistatin. As the hallmark of pregnancy, progesterone is one of the essential hormones in maternal blood with significant roles in decreasing fetomaternal response (Beagley and Gockel 2003). Various studies have demonstrated the protective role of high progesterone levels in the survival of allogeneic and xenogeneic grafts (Szekeres-Bartho 2002). This function is mediated by inhibiting the antibody release, suppressing T-cell cytotoxicity and activation, stimulating matrix metalloproteinase, activating adhesion molecules, modifying NK cell activity, and inducing protective asymmetric antibody secretion (Kyurkchiev et al. 2010). Human endogenous retroviruses (HERVs), representing approximately 8% of the whole genome, have a very high expression level in the placenta and embryonic tissues. Various functions have been explained for HERVs, and their role in fetomaternal tolerance has attracted significant attention (Mangeney et al. 2007). The immunosuppressive domain (ISD) of HERVs in the transmembrane subunit of the envelope protein in most retroviruses also shows an immunosuppressive property. Syncytin-1 and syncytin-2 have some degrees of homology with ISD. Moreover, placenta exosomes may have a major function in maternal immune tolerance (Mincheva‐Nilsson and Baranov 2010).