Abstract
During gestation, many different mechanisms act to render the maternal immune system tolerant to semi-allogeneic trophoblast cells of foetal origin, including those mediated via mucins that are expressed during the peri-implantation period in the uterus. Tumour- associated glycoprotein-72 (TAG-72) enhances the already established tolerogenic features of decidual dendritic cells with the inability to progress towards Th1 immune orientation due to lowered interferon (IFN)-γ and interleukin (IL)-15 expression. Mucine 1 (Muc 1) supports alternative activation of decidual macrophages, restricts the proliferation of decidual regulatory CD56+ bright natural killer (NK) cells, and downregulates their cytotoxic potential, including cytotoxic mediator protein expression. Removing TAG-72 and Muc 1 from the eutopic implantation site likely contributes to better control of trophoblast invasion by T cells and NK cells and appears to have important immunologic advantages for successful implantation, in addition to mechanical advantages. However, these processes may lead to uncontrolled trophoblast growth after implantation, inefficient defence against infection or tumours, and elimination of unwanted immunocompetent cells at the maternal-foetal interface. The use of mucins by tumour cells to affect the local microenvironment in order to avoid the host immune response and to promote local tumour growth, invasion, and metastasis confirms this postulation.
Highlights
The mother and conceptus are engaged in a chemical conversation throughout pregnancy [1]
Tumour- associated glycoprotein-72 (TAG-72) enhances the already established tolerogenic features of decidual dendritic cells with the inability to progress towards Th1 immune orientation due to lowered interferon (IFN)-γ and interleukin (IL)-15 expression
Removing TAG-72 and Mucine 1 (Muc 1) from the eutopic implantation site likely contributes to better control of trophoblast invasion by T cells and natural killer (NK) cells and appears to have important immunologic advantages for successful implantation, in addition to mechanical advantages
Summary
The mother and conceptus are engaged in a chemical conversation throughout pregnancy [1]. Cycling endometrium provides a microenvironment in which molecules secreted by uterine cells, including glycoproteins mucin-1- (Muc 1-) and tumour-associated glycoprotein-72 (TAG-72), are transported into the uterine lumen, where they represent histotrophs required for blastocyst growth and development [2]. The blastocyst forms directly under uterine influence after its apposition and adhesion to the receptive endometrium [2, 3]. Chemokines, and growth factors expressed by decidual cells, with their pleiotropic and redundant functions, are broadly involved in stimulating growth, differentiation, and the function of uterine and trophoblast cells, as well as in their mutual coordination and synchronization [2, 4]. Blois et al [5] showed that pregnancy-specific glycoproteins influence trophoblast immune evasion. Many studies in animal and human models failed to completely elucidate mucinmediated immunophysiological and immunopathological pathways involved in establishing pregnancy
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