Factors Biological action References
IL33 IL33 regulates the factors essential for decidual receptivity during the implantation window. [119]
IL11 It is a vital cytokine associate with decidualization, implantation as well as placentation. [119, 165-167]
dNK cells They primarily support the trophoblasts incursion and vascular modification to facilitate the maximization of the process of placental perfusion which is possibly under the control of cytokine and chemokines expression. [229, 230]
IFNγ It causes the activation of macrophages present in decidua which in turn manufacture the factors such as NO and TNFα that may well cause pregnancy loss. [234-236]
IL4 and IL10 They could impede the functions both of Th1 type of cells as well as macrophages that prevent the feto-allograft dismissal. [234-236]
IFNγ, IL4, IL6, TNFα, TGFβ, M-CSF and LIF receptors These receptors existing on the surface of trophoblastic cells could mediate the effect of cytokines produced by T cells directly on the growth and role of trophoblasts. [234-236]
M-CSF (macrophage colony stimulating factor) This factor is responsible for inciting trophoblast proliferation in addition of the formation of syncytium from cytotrophoblast via differentiation process. [237, 238]
LIF(Leukemia-inhibitory factor) Essential for endometrial implantation and fetal development. [239]
IL8 One of the pro-angiogenic cytokines responsible for stimulating endothelial cell proliferation and capillary tube formation. [309]
IL10 Expressed at materno-embryonic interface and inhibits the formation and role of proinflammatory cytokines such as IL1, IL12, IFNγ etc. It also stimulates the tolerogenic dendritic cell production [24, 241-243, 245]
IL15 This interleukin is considered as a key factor for stimulating in-vivo proliferation of uNK cells. [183]
TNFα and IFNγ They hamper the development of embryo and the production of trophoblasts lineages in human due to their cytotoxic effect on the embryonic fibroblast like cells. [255, 256]
TNFα During pregnancy it along with hormones brings about thrombosis in placental tissue and shows increased synthesis at the time of onset of labor and miscarriage. [286]
TNFα has been found linked with the process of inflammation associated with implantation, placentation, and pregnancy outcome. [224]
Foxp3 Mrna Diminished expression in endometrial tissue is linked with primary idiopathic infertility. [300]
The trophoblasts of RPL patients show decreased expression of Foxp3 [301]
Treg cells They down regulate the inflammatory responses and protects the developing embryo. Further, they impede the cytokine synthesis in CD4+ and CD8+ T cells, cytotoxicity of Natural killer cells and dendritic cell maturation and function as a result of which the activation of local inflammation is suppressed. In absence of the Treg cell mediated modulation there is the possibility of collapse of pregnancy. [9, 302-304]
Decreased percentage of decidual Treg cells has been associated with miscarriage pathogenesis. [310]
The materno-embryonic tolerance mediated by Treg cells has been reported critical for the establishment allogenic pregnancy. [310]
Micro-RNA (miR-155) The reduced level of immune-regulatory microRNA miR-155 has been observed in RPL which suggests the role of miR-155 in immune tolerance during pregnancy. miR-155 is a vital regulator of immune adaptation to pregnancy and is essential for adequate Treg cell to attain strong pregnancy tolerance and protect against embryonic loss. [311]
Endometrial EGR1 The decreased levels of EGR1 have been observed in women that experience recurrent implantation failure. [10]