Production of leukemia inhibitory factor (LIF) by T cells associates with type 2T helper (Th2) cytokines. Defective production of both by decidual T cells in unexplained recurrent abortions

Institute of Internal Medicine and Immunoallergology, University of Florence, Italy.
Nature Medicine (Impact Factor: 27.36). 10/1998; 4(9):1020-4. DOI: 10.1038/2006
Source: PubMed


Leukemia inhibitory factor is essential for embryo implantation, and a shift from type 1 T-helper to type 2 T-helper response at the fetal-maternal interface may contribute to successful pregnancy. We show that LIF production is associated with type 2 T-helper cells, is upregulated by IL-4 and progesterone and is downregulated by IL-12, IFN-gamma and IFN-alpha. We also show a decreased production of LIF, IL-4 and IL-10 by decidual T cells of women with unexplained recurrent abortions in comparison with that of women with normal gestation. The defective production of LIF and/or type 2 T-helper cytokines may contribute to the development of unexplained recurrent abortions.

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Available from: Marie-Pierre Piccinni, Apr 21, 2015
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    • "Evidence suggests that the mean of the Th1:Th2 ratio in patients with RPL and in patients with multiple implantation failure after IVF-embryo transfer [188] is significantly higher than in normal fertile women. This predominance of Th1 cytokines was demonstrated to exist in endometrial cells as well as peripheral blood mononuclear cells before pregnancy [187] [189] [190] and at the time of miscarriage in decidual cells [191]. However, there are significant discrepancies in the results of the different studies, as some suggest that Th1 cytokines production was higher in normal women than in RPL patients in early pregnancy [192], and others even found that the production of Th1 and Th2 cytokines was similar in RPL patients who subsequently had successful or failed pregnancies [193]. "
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    ABSTRACT: Embryo implantation depends on both embryo quality and the endometrial environment. Implantation failure has a complex, variable pathophysiology and is detrimental to the outcome of in vitro fertilization (IVF). Thus, patients with multiple implantation failure require an individualized approach to diagnosing and managing treatment options for future IVF cycles. These options should be based on concrete, unambiguous, consistent scientific evidence with random-ized, controlled trials. We review and discuss 14 treatment options: (i) blastocyst transfer, (ii) assisted hatching, (iii) co-culture, (iv) preimplanta-tion genetic screening, (v) hysteroscopy, (vi) sildenafil, (vii) salpingectomy for tubal disease, (viii) oocyte donation, (ix) transfer of six or more embryos, (x), intratubal embryo transfer, (xi) natural cycle IVF, (xii) antiphospholipid antibodies (APA) testing and treatment, (xiii) allogenic lymphocyte therapy, and (xiv) IV immunoglobin therapy. The approaches were evaluated based on available information from studies, expert opinions, consensus, etc. We conclude that blastocyst transfer, assisted hatching, salpingectomy for tubal disease, and hysteroscopy in IVF procedures are clinically effective. This review serves as a summary of current treatment options for clinicians to counsel patients and manage their expectations based on strong and reliable evidence.
    Full-text · Chapter · Jan 2014
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    • "Although production of some cytokines (IL-13, TNF-a, GM-CSF, IL-6) derived from TCCs generated from tissue controls of patients with reticular OLP appeared higher than TCCs generated from tissue controls of patients with erosive OLP (Figure 2), other cytokines (and in particular IL-17) produced by TCCs derived from tissue controls of patients with reticular OLP statistically did not differ from those produced by TCCs derived from tissue controls of patients with erosive OLP. A TCC, which consists of more than 10 6 cells, is derived from a single T cell that grows in culture with a recombinant T-cell growth factor (rIL-2) and feeder cells (irradiated fresh allogeneic peripheral blood mononuclear cells from different healthy donors) (Piccinni et al, 1998), which support the T-cell culture for 2 months. For a certain tissue specimen, the feeder cells used for all the cultures are the same for both lesional tissues and the tissue controls, because the two T-cell clonings are performed together in the same conditions. "
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    ABSTRACT: Objectives: The role of Th17 cells and associated cytokines was investigated in oral lichen planus. Material and methods: 14 consecutive patients with oral lichen planus were investigated. For biological studies, tissues were taken from reticular or erosive lesions and from normal oral mucosa (controls) of the same patient. mRNA expression for IL-17F, IL-17A, MCP-1, IL-13, IL-2, IL-10, IL-1β, RANTES, IL-4, IL-12B, IL-8, IFN-γ, TNF-α, IL-1α, IL-18, TGF-β1, IL-23R, IL-7, IL-15, IL-6, MIG, IP-10, LTB, VEGF, IL-5, IL-27, IL-23A, GAPDH, PPIB, Foxp3, GATA3, and RORC was measured using the QuantiGene 2.0. Results: Results showed that Th17-type and Th0-type molecules' mRNAs, when compared with results obtained from tissue controls, were increased in biopsies of erosive lesions, whereas Th2-type molecules' mRNAs were increased in reticular lesions. When the CD4+ T-cell clones, derived from oral lichen planus tissues and tissue controls, were analyzed, a higher prevalence of Th17 (confirmed by an increased CD161 expression) and Th0 CD4+ T clones was found in erosive lesions, whereas a prevalence of Th2 clones was observed in reticular lesions. Conclusions: Our data suggest that Th17, Th0, and Th2 cells, respectively, may have a role in the pathogenesis of erosive and reticular oral lichen planus.
    Full-text · Article · Mar 2013 · Oral Diseases
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    • "A direct relationship between the defective production of LIF and pregnancy loss is associated with recurrent implantation failure [44], [45]. It has been reported that T cells from recurrent aborter women secrete less LIF than those from normal women [46]. Infertile women also have lower levels of expression of endometrial LIF [45]. "
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    ABSTRACT: Lipopolysaccharide (LPS) administration to mice on day 7 of gestation led to 100% embryonic resorption after 24 h. In this model, nitric oxide is fundamental for the resorption process. Progesterone may be responsible, at least in part, for a Th2 switch in the feto-maternal interface, inducing active immune tolerance against fetal antigens. Th2 cells promote the development of T cells, producing leukemia inhibitory factor (LIF), which seems to be important due to its immunomodulatory action during early pregnancy. Our aim was to evaluate the involvement of progesterone in the mechanism of LPS-induced embryonic resorption, and whether LIF can mediate hormonal action. Using in vivo and in vitro models, we provide evidence that circulating progesterone is an important component of the process by which infection causes embryonic resorption in mice. Also, LIF seems to be a mediator of the progesterone effect under inflammatory conditions. We found that serum progesterone fell to very low levels after 24 h of LPS exposure. Moreover, progesterone supplementation prevented embryonic resorption and LPS-induced increase of uterine nitric oxide levels in vivo. Results show that LPS diminished the expression of the nuclear progesterone receptor in the uterus after 6 and 12 h of treatment. We investigated the expression of LIF in uterine tissue from pregnant mice and found that progesterone up-regulates LIF mRNA expression in vitro. We observed that LIF was able to modulate the levels of nitric oxide induced by LPS in vitro, suggesting that it could be a potential mediator of the inflammatory action of progesterone. Our observations support the view that progesterone plays a critical role in a successful pregnancy as an anti-inflammatory agent, and that it could have possible therapeutic applications in the prevention of early reproductive failure associated with inflammatory disorders.
    Full-text · Article · Feb 2013 · PLoS ONE
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