The Possible Role of the JAK/STAT Pathway in Lymphocytes at the Fetomaternal Interface

Abstract

Pregnancy is accompanied by a Th2-prone immune modulation, which is a major puzzle piece among maternofetal tolerance-promoting factors. A large number of cytokines is physiologically or pathologically present in the decidua and is potentially able to act on lymphocytes and NK cells, which express a variety of respective receptors. Intracellular signals from these receptors are to a major part transduced via the Janus kinases (JAK) and signal transducers and activators of a transcription (STAT) system, which consists of at least 4 different kinases and 7 STATs plus several subtypes and splicing variants. A network of suppressors of cytokine signaling (SOCS) controls their balance. The interactions of all these intracellular factors and cross-linking with further signaling systems seem to be crucial for the maintenance of a maternal cytokine profile which promotes the tolerance of the fetus.

Human embryo immune escape mechanisms rediscovered by the tumor

“…Intracellular signals from these receptors are, for the most part, transduced via Janus kinases (JAK), signal transducers and activators of a transcription system (STAT), which consist of several different kinases (Wegmann et al, 1993;Sacks et al, 2000;Poehlmann et al, 2005). The production of IL-4 and IL-10, IL-5, PGE2, and M-CSF by cells of the uterus may be responsible for the lack of response to fetal antigens by Th1, but may also explain the induction of a Th2 response, which results in anergy (Piccinni et al, 1995(Piccinni et al, , 2000Piccinni and Romagnani, 1996;Saito, 2000).…”

Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

“…Furthermore, studies have shown that galectin-1 (Blois et al, 2007) and indoleamine 2,3-dioxygenase (Munn et al, 1998) play pivotal roles in maternal-fetal tolerance. Wnt, PD-L1, signal transducers, activators of transcription (STAT) 3 and stimulatory (CD80 and CD86) signals also participate in the regulation of pregnancy (Guleria et al, 2005;Poehlmann et al, 2005;Zhang et al, 2009). It has become increasingly acknowledged that NK cells are pivotal in maternal adaption to pregnancy as they are the largest population of immune cells during the first trimester in human deciduas and show a close reaction to invasive fetal trophoblasts and stromal cells (Colucci and Kieckbusch, 2015;Tao et al, 2015).…”

Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal–fetal interface

“…For example, T H 2 cytokine polarization (6)(7)(8)(9), the expression of the Fas ligand on trophoblast cells (10), and the inhibition of complement activation (11) are crucial for ensuring tolerance at the maternal-fetal interface. In addition, a delicate balance exists between inhibitory (PD-L1, Stat3, and TGF-β1) and stimulatory (CD80 and CD86) signals during the establishment of immune privilege (12)(13)(14)(15)(16)(17)(18). Furthermore, studies have shown that galectin-1 (19) and indoleamine 2,3-dioxygenase (20) play pivotal roles in maternal-fetal tolerance.…”