Human decidual natural killer cells as a source and target of macrophage migration inhibitory factor

Abstract

The human uterine mucosa of early pregnancy is largely populated by CD56 bright natural killer (NK) cells (uterine (u) NK cells). The specific functions of these cells are still unknown, but their interaction and response to foetal trophoblasts are thought to be important for the establishment of a successful pregnancy. The study reported herein shows that uNK cells respond to, and produce, macrophage migration inhibitory factor (MIF), a cytokine highly expressed in the human placenta and in the cyclic and pregnant endometrium. Recombinant human MIF reduced in a dose-dependent manner the cytolytic activity of purified uNK cells against K562 cells. RT-PCR, Western blot analysis and ELISA demonstrated the synthesis and secretion of the cytokine by uNK cells. Double immunofluorescence staining showed the presence of MIF in uterine CD56 1 cells. Finally, neutralization of the endogenous cytokine by a polyclonal antibody resulted in a sharp increase in the cytolytic activity of uNK cells. These findings indicate the existence of a previously unrevealed paracrine and autocrine action of MIF on uNK cells and support its contribution to the immune privilege at the maternal-foetal interface.

NK Cells, Autoantibodies, and Immunologic Infertility: A Complex Interplay

“…Macrophage migration inhibitory factor (MIF), the first cytokine to be discovered, is now recognized as an inhibitor of the random migration of macrophages in vitro and can affect several biological functions of macrophages such as phagocytosis and killing of intracellular parasites and tumor cells exerting both an autocrine and a paracrine modulatory action on UNK cell activity. MIF may contribute to the immune privilege at the maternal-fetal interface [46].…”

The Role of Glucocorticoids in Pregnancy: Four Decades Experience with Use of Betamethasone in the Prevention of Pregnancy Loss

“…Moreover, they are up-regulated by low oxygen tension, comparable to the values occurring at the very early stage of pregnancy (Ietta et al, 2007). Trophoblast MIF reduces the cytotoxicity of decidual natural killer (NK) cells (Arcuri et al, 2006), and intraperitoneal injection of rMIF to pregnant mice induces an increase of endometrial alpha(v),beta-3-integrin subunits and VEGF expression, that are markers of uterine receptivity (Bondza et al, 2008). Accordingly, pregnant MIF-treated mice show an enhanced rate of implanted embryos with respect to controls (Bondza et al, 2008), although fertility is not impaired in MIF knock-out mice (Fingerle-Rowson et al, 2003).…”

Immune Privilege Collapse and Alopecia Development: Is Stress a Factor

“…Macrophage migration inhibitory factor (MIF) expression is increased in the proximal follicular epithelium compared to the distal follicle [6]. With a location near the vital eHF-SC population, MIF is thought to contribute to HFIP via its immunomodulating properties and suppression of NK attack [35,56,57].…”