CTLA4Ig gene transfer alleviates abortion in mice by expanding CD4+CD25+ regulatory T cells and inducing indoleamine 2,3-dioxygenase

Li, Weihong; Li, Bin; Fan, Wei; Geng, Lihua; Li, Xiaohong; Li, Lei; Huang, Zhongying; Li, Shangwei

doi:10.1016/j.jri.2008.11.006

Cited by 29 publications

(24 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IDO1 is highly expressed in the placenta, and exposure of pregnant mice to the IDO1 inhibitor 1-MT caused the rejection of foetuses from allogeneic but not syngeneic matings in a manner that was dependent on maternally derived T-cells and complement activation [217,269]. Induction of IDO1 by soluble CTLA-4-Ig in abortion-prone mice improves the pregnancy outcome [270], suggesting that IDO1 expression at the foetal/maternal interface acts to protect the immunologically foreign foetus from maternal immune attack. Accordingly, in humans, active IDO1 is variably expressed during several stages of pregnancy in placental syncytiotrophoblasts, extravillious cytotrophoblasts, macrophages in the villous stroma, vascular endothelium and foetal membranes [48,271].…”

Section: Ido1 and Immune Regulation In Physiological And Disease Settmentioning

confidence: 99%

Role of indoleamine 2,3-dioxygenase in health and disease

et al. 2015

View full text Add to dashboard Cite

IDO1 (indoleamine 2,3-dioxygenase 1) is a member of a unique class of mammalian haem dioxygenases that catalyse the oxidative catabolism of the least-abundant essential amino acid, L-Trp (L-tryptophan), along the kynurenine pathway. Significant increases in knowledge have been recently gained with respect to understanding the fundamental biochemistry of IDO1 including its catalytic reaction mechanism, the scope of enzyme reactions it catalyses, the biochemical mechanisms controlling IDO1 expression and enzyme activity, and the discovery of enzyme inhibitors. Major advances in understanding the roles of IDO1 in physiology and disease have also been realised. IDO1 is recognised as a prominent immune regulatory enzyme capable of modulating immune cell activation status and phenotype via several molecular mechanisms including enzyme-dependent deprivation of L-Trp and its conversion into the aryl hydrocarbon receptor ligand kynurenine and other bioactive kynurenine pathway metabolites, or non-enzymatic cell signalling actions involving tyrosine phosphorylation of IDO1. Through these different modes of biochemical signalling, IDO1 regulates certain physiological functions (e.g. pregnancy) and modulates the pathogenesis and severity of diverse conditions including chronic inflammation, infectious disease, allergic and autoimmune disorders, transplantation, neuropathology and cancer. In the present review, we detail the current understanding of IDO1's catalytic actions and the biochemical mechanisms regulating IDO1 expression and activity. We also discuss the biological functions of IDO1 with a focus on the enzyme's immune-modulatory function, its medical implications in diverse pathological settings and its utility as a therapeutic target.

show abstract

Section: Ido1 and Immune Regulation In Physiological And Disease Settmentioning

confidence: 99%

Role of indoleamine 2,3-dioxygenase in health and disease

et al. 2015

View full text Add to dashboard Cite

show abstract

“…C Treg population (Li et al 2009). Finally, LIF has also been involved in graft acceptance and alloantigen-driven tolerance, whereas Tregs release high levels of LIF (Metcalfe et al 2005, Zenclussen et al 2006.…”

Section: Cd25mentioning

confidence: 99%

Potential immunomodulatory role of VIP in the implantation sites of prediabetic nonobese diabetic mice

Roca¹,

Calafat²,

Larocca³

et al. 2009

Reproduction

View full text Add to dashboard Cite

Among several factors known to modulate embryo implantation and survival, uterine quiescence and neovascularization, maternal immunotolerance through the Th1/Th2 cytokine balance towards a Th2 profile, local regulatory T-cell (Treg) activation, and high levels of progesterone were assigned a prominent role. Vasoactive intestinal peptide (VIP) is a neuroimmunopeptide that has anti-inflammatory effects, promotes Th2 cytokines and CD4C Treg activation, and stimulates exocrine secretion, smooth muscle relaxation, and vasodilatation favoring uterus quiescence. The goal of the present work was to explore the participation of VIP in the implantation sites of normal and pregnant prediabetic nonobese diabetic (NOD) females, a mouse strain that spontaneously develops an autoimmune exocrinopathy similar to Sjö gren's syndrome. Our results indicate a reduction in litter size from the third parturition onwards in the NOD female lifespan with increased resorption rates. Progesterone systemic levels were significantly decreased in pregnant NOD mice compared with BALB/c mice, although the allogeneic response to progesterone by spleen cells was not impaired. VIP receptors, Vipr1 and Vipr2 (Vpac1 and Vpac2), were expressed at the implantation sites and VIP induced leukemia inhibitory factor (LIF) and Treg marker expression in both strains; however, a reduced Vip expression was found in NOD implantation sites. We conclude that the reduced birth rate at 16-week-old NOD mice with a Th1 systemic cytokine profile involves resorption processes with a lower expression of VIP at the sites of implantation, which acts as a local inducer of pro-implantatory LIF and Treg activation.

show abstract

“…170 The use of anti-CTLA4 antibody therapy with CD80/CD86 blockade has been found to regulate the Th2/Th1 balance in PBMCs isolated from women with recurrent spontaneous abortion, which lead to the design of an adenoviral cytotoxic T lymphocyte antigen 4 (CTLA4) antibody that showed improved pregnancy outcomes in a mouse model of spontaneous abortion. 171,172 …”

Section: Reversing Tolerance In Melanomamentioning

confidence: 99%

Immunomodulatory Effects of Sex Hormones: Requirements for Pregnancy and Relevance in Melanoma

Enninga

Holtan

Creedon

et al. 2014

Mayo Clinic Proceedings

View full text Add to dashboard Cite

Similarities between the pathologic progression of cancer and the physiologic process of placentation (e.g., proliferation, invasion, and local/systemic tolerance) have been recognized for many years. Sex hormones such as human chorionic gonadotropin, estrogens, progesterone, and others contribute to induction of immunologic tolerance at the beginning of gestation. Sex hormones have been shown to play contributory roles in the growth of cancers such as breast, prostrate, endometrial and ovarian cancer, but their involvement as putative mediators of the immunologic escape of cancer are still being elucidated. Herein, we compare the emerging mechanism by which sex hormones modulate systemic immunity in pregnancy and their potentially similar role in cancer. To do this, we conducted a PubMed search using combinations of the following key words: immune regulation, sex hormones, pregnancy, melanoma and cancer. We did not limit our search to specific publication dates. Mimicking the maternal immune response to pregnancy, especially in late gestation, might aid in design of better therapies to reconstitute endogenous anti-tumor immunity and improve survival.

show abstract

CTLA4Ig gene transfer alleviates abortion in mice by expanding CD4+CD25+ regulatory T cells and inducing indoleamine 2,3-dioxygenase

Cited by 29 publications

References 47 publications

Role of indoleamine 2,3-dioxygenase in health and disease

Role of indoleamine 2,3-dioxygenase in health and disease

Potential immunomodulatory role of VIP in the implantation sites of prediabetic nonobese diabetic mice

Immunomodulatory Effects of Sex Hormones: Requirements for Pregnancy and Relevance in Melanoma

Contact Info

Product

Resources

About