Indoleamine 2,3-dioxygenase levels at the normal and recurrent spontaneous abortion fetal–maternal interface

Ban, Yanli; Chang, Yongchun; Dong, Bo; Kong, Beihua; Qu, Xun

doi:10.1177/0300060513487642

Cited by 45 publications

(37 citation statements)

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“…Though a review of the impact of kynurenine metabolism on the peripheral immune system is beyond the scope of the current review, it is important to keep this function of the kynurenine system in mind when considering the therapeutic potential of this pathway. An important role of IDO in immunosuppression and tolerance has been demonstrated during pregnancy, autoimmunity, resistance to tumors, and tolerance to allografts (Mellor and Munn, 2004; Barth and Raghuraman, 2012; Ban et al, 2013). Thus, therapeutic interventions involving the KP must be approached cautiously to examine the potential consequence on immunomodulatory actions.…”

Section: Therapeutic Potential and Immune Interactions By The Kynurenmentioning

confidence: 99%

Kynurenines in CNS disease: regulation by inflammatory cytokines

et al. 2014

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The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the “neurotoxic” and “neuroprotective” arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders.

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Section: Therapeutic Potential and Immune Interactions By The Kynurenmentioning

confidence: 99%

Kynurenines in CNS disease: regulation by inflammatory cytokines

et al. 2014

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“…The constitutive expression of HLA-G on these cells plays an important role in inducing immunotolerance by inhibiting cytotoxicity mediated by natural killer (NK) cells [3-6] and T-cells [7-9]. In addition, the finding of decreased protein and mRNA levels of indoleamine 2,3-dioxygenase (IDO) in the placenta and decidua from recurrent spontaneous abortuses suggests an important role for IDO in the maintenance of normal pregnancy [10]. It has also been suggested that during pregnancy the programmed cell death-1 (PD-1) pathway can modify the maternal decidual lymphocyte cytokine secretion facilitating immune suppression[11].…”

Section: Introductionmentioning

confidence: 99%

PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases

Veras

Kurman²,

Wang³

et al. 2017

International Journal of Gynecological Pathology

160

112

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One of the major immune checkpoints responsible for immune evasion in cancer cells is the interaction between programmed cell death-1 (PD-1) and its ligand (PD-L1). Since human trophoblastic cells display many of the features of malignant cells such as the ability to invade normal tissue including blood vessels and are apparently not eradicated by the host immune system, we undertook the present study to determine whether PD-L1 was upregulated in different types of trophoblastic cells during normal pregnancy and in gestational trophoblastic diseases. Immunohistochemistry using an anti-PD-L1 specific antibody demonstrated that in early and term normal placentas, PD-L1 was highly expressed in syncytiotrophoblast and to a much lower extent in intermediate trophoblastic cells located in the chorion laeve and implantation site. PD-L1 immunoreactivity was undetectable in cytotrophoblastic cells. This staining pattern in normal placenta was recapitulated in various types of gestational trophoblastic disease. PD-L1 was highly expressed by syncytiotrophoblast in complete moles and choriocarcinomas. The intermediate trophoblastic neoplasms, placental site trophoblastic tumors and epithelioid trophoblastic tumors, showed variable PD-L1 immunoreactivity but at a lower intensity than in the neoplastic syncytiotrophoblast in choriocarcinoma. In addition, we observed PD-1 positive lymphocytes located within the implantation site and in trophoblastic tumors. In summary, this study describes a novel mechanism for trophoblastic cells to create a tolerogenic feto-maternal interface by upregulating PD-L1 in syncytiotrophoblast and in intermediate trophoblast. Trophoblastic tumors may also use PD-L1 expression to evade the host immune response thereby promoting their survival.

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“…They are poorly characterized with regard to their distinctive phenotype, anatomical localization, and function, however, appear to be important in embryo implantation and, most likely, in regulating placenta-specific tolerance to the semiallograft [28,40,41]. There are several reports documenting that DCs conditioned by trophoblasts in vitro fail to promote expansion of T cells or stimulate differentiation of regulatory T cells, which was mainly attributed to the production of soluble mediators such as IDO, TSLP,33,42,43]. Though we cannot exclude that soluble mediators may contribute in DC silencing by choriocarcinoma cells in our system, these are unlikely to contribute in cocultures involving CHO transfectants, which would only release hamster-specific factors not triggering a response in human target cells.…”

mentioning

confidence: 99%

Human endogenous retrovirus envelope proteins target dendritic cells to suppress T‐cell activation

et al. 2015

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Though mostly defective, human endogenous retroviruses (HERV)can retain open reading frames, which are especially expressed in the placenta. There, the envelope (env) proteins of HERV-W (Syncytin-1), HERV-FRD (Syncytin-2), and HERV-K (HML-2) were implicated in tolerance against the semi-allogenic fetus. Here, we show that the known HERV envbinding receptors ASCT-1 and -2 and MFSD2 are expressed by DCs and T-cells. When used as effectors in coculture systems, CHO cells transfected to express Syncytin-1, -2, or HML-2 did not affect T-cell expansion or overall LPS-driven phenotypic DC maturation, however, promoted release of IL-12 and TNF-α rather than IL-10. In contrast, HERV env expressing choriocarcinoma cell lines suppressed T-cell proliferation and LPS-induced TNF-α and IL-12 release, however, promoted IL-10 accumulation, indicating that these effects might not rely on HERV env interactions. However, DCs conditioned by choriocarcinoma, but also transgenic CHO cells failed to promote allogenic T-cell expansion. This was associated with a loss of DC/T-cell conjugate frequencies, impaired Ca 2+ mobilization, and aberrant patterning of f-actin and tyrosine phosphorylated proteins in T-cells. Altogether, these findings suggest that HERV env proteins target T-cell activation indirectly by modulating the stimulatory activity of DCs.Keywords: DCs r DC/T-cell conjugates r HERV r Immune tolerance r Immunological synapse r T-cell activation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHuman endogenous retroviruses (HERVs) are estimated to comprise about 8% of the human genome [1]. They are mainly germline transmitted. HERVs are typically defective as a result of multiple mutations in their genomes, and it is therefore only on exception that viral particles can be produced [1,2]. Endogenous retroviruses (ERVs) can substantially regulate host cell gene expression and functions. In addition to viral transcripts, ERV encoded proteins translated from intact ORFs were implicated Correspondence: Dr. Sibylle Schneider-Schaulies e-mail: s-s-s@vim.uni-wuerzburg.de in both pathological and physiological processes [3]. The latter has for instance been revealed for the envelope (env) regions of three HERVs (ERV-3, HERV-W, and HERV-FRD). These are highly expressed in early and late placentae, and their importance in successful accomplishment of pregnancy has been suggested [4][5][6][7][8][9][10], not least because spontaneous abortions or complications of gestation like preeclampsia are associated with reduced levels of HERV env proteins [11,12]. In fact, their expression has been found crucial in the intrauterine fetal development in promoting syncytiotrophoblast formation, while the HERV-FRD env was also associated with fetomaternal tolerance to prevent rejection of the fetus [13][14][15][16][17].Immunodeficiency is commonly associated with retroviral infections (for a recent review see [18] effector mechanisms studied, immunosuppressive domains (ISD) we...

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Indoleamine 2,3-dioxygenase levels at the normal and recurrent spontaneous abortion fetal–maternal interface

Cited by 45 publications

References 45 publications

Kynurenines in CNS disease: regulation by inflammatory cytokines

Kynurenines in CNS disease: regulation by inflammatory cytokines

PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases

Human endogenous retrovirus envelope proteins target dendritic cells to suppress T‐cell activation

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