Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

Tripathi, Sudipta; Guleria, Indira

doi:10.4103/2319-4170.143511

Cited by 44 publications

(10 citation statements)

References 74 publications

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“…Engagement of PD-L1 with its receptor, PD-1 on T cells leads to the promotion of Treg development and function and down-regulation of T-cell responses. The interactions between PD-1 and PD-L1 participate in the maintenance of pregnancy partly by regulating Treg- and Th17-immunity 29 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Apart from autoimmune disorders, this pathway has been proven to be involved in the establishment of maternal-fetal tolerance 26 27 , since PD-L1 blockade results in the reduction in litter size, number and increase in embryo resorption of mice, and the failure of fetal–maternal tolerance with Treg deficiency and hyperactivity of Th17 cells 28 . Therefore, the altered PD-1/PD-L1 pathway may be associated with the Treg/Th17 imbalance in human pregnancy 29 30 . The PD-1/PD-L1 pathway is considered a particularly attractive therapeutic target in autoimmune diseases, because the development of PD-1 agonists could deliver the necessary ‘one-two punch’ to protect against self-reactivity: (I) augmenting iTreg function and (II) concomitantly suppressing the expansion and functions of activated effector T cells 20 .…”

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confidence: 99%

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The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats

Tian

Zhang

Liu

et al. 2016

Sci Rep

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The programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis by promoting regulatory T (Treg) development and inhibiting effector T (such as Th17) cell responses. However, the association between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance has not been fully investigated in pre-eclampsia (PE). In this study, we observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 on the two subsets also changed in PE compared with normal pregnancy. We further explored their relationship in vivo using the L-NG-Nitroarginine Methyl Ester (L-NAME) induced PE-like rat models, also characterized by Treg/Th17 imbalance. Administration of PD-L1-Fc protein provides a protective effects on the pre-eclamptic models, both to the mother and the fetuses, by reversing Treg/Th17 imbalance through inhibiting PI3K/AKT/m-TOR signaling and enhancing PTEN expression. In addition, we also observed a protective effect of PD-L1-Fc on the placenta by reversing placental damages. These results suggested that altered PD-1/PD-L1 pathway contributed to Treg/Th17 imbalance in PE. Treatment with PD-L1-Fc posed protective effects on pre-eclamptic models, indicating that the use of PD-L1-Fc might be a potential therapeutic target in PE treatment.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats

Tian

Zhang

Liu

et al. 2016

Sci Rep

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“…Our working hypothesis is that NPI and SELTA through engagement of TLR2 increase PDL1/2 expression. The increased ligands serve to directly repress activated CD4+ve T-cells, including Th17 cells, via PD1, while also inducing IL10 expression [43]. IL10 can then act to reverse EAP-induced increases in IL17 via either direct expansion or increased activity of T-regs.…”

Section: Discussionmentioning

confidence: 99%

Commensal bacterial modulation of the host immune response to ameliorate pain in a murine model of chronic prostatitis

Murphy

Schaeffer²,

Done³

et al. 2017

PAIN

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The human commensal microflora plays an essential role in modulating the immune response to control homeostasis. Staphylococcus epidermidis, a commensal bacteria most commonly associated with the skin exerts such effects locally, modulating local immune responses during inflammation and preventing superinfection by pathogens such as Staphylococcus aureus. While the prostate is considered by many to be sterile, multiple investigations have shown that small numbers of gram-positive bacterial species such as S. epidermidis can be isolated from the expressed prostatic secretions (EPS) of both healthy and diseased men. Chronic pelvic pain syndrome (CPPS) is a complex syndrome with symptoms including pain and lower urinary tract dysfunction (LUTs). It has an unknown etiology and limited effective treatments but is associated with modulation of prostate immune responses. CPPS can be modeled using murine experimental prostatitis (EAP) where CD4+ve IL17A+ve T-cells have been shown to play a critical role in disease orchestration and development of pelvic tactile allodynia. Here we report that intra-urethral instillation of a specific S. epidermidis strain (designated NPI (non pain-inducing)), isolated from the EPS of a healthy human male, into EAP treated mice reduced the pelvic tactile allodynia responses and the increased CD4+ve IL17A+ve T-cell numbers associated with EAP. Furthermore, a cell wall constituent of NPI, lipotechoic acid (LTA), specifically recapitulates these effects and mediates increased expression of CTLA4-like ligands PDL1 and PDL2 on prostatic CD11b+ve antigen presenting cells. These results identify a new potential therapeutic role for commensal S. epidermidis NPI LTA in the treatment of prostatitis-associated pain.

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“…PD-1 is also able to directly promote interleukin-10 (IL-10) secretion by T cells ( 23 ) and inhibit the maturation of DCs ( 24 ). PD-L1/PD-1 interaction shows a critical role also for the establishment of fetus tolerance ( 25 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Receptors and Pathways of Lymphocytes: The Role of PD-1 in Treg Development and Their Involvement in Autoimmunity Onset and Cancer Progression

2018

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Regulatory T (Treg) cells represent a subpopulation of suppressor CD4+ T cells critically involved in the establishment of peripheral tolerance through the inhibition of effector T (Teff) cells and the suppression of the immune-mediated tissue destruction toward self-antigens. Treg generation, their suppressive properties and also Treg-Teff cell interactions could be modulated at least in part by programmed cell death-1 (PD-1) expression on their surface and through binding between PD-1 and programmed cell death ligand-1 (PD-L1). Defects involving PD-1 and Tregs can lead to the development of pathological conditions, including autoimmune disorders or promote cancer progression by favoring tumor evasion from the host immune response. At the same time, PD-1 and Tregs could represent attractive targets for treatment, as demonstrated by the therapeutic blockade of PD-L1 applied for the management of different cancer conditions in humans. In the present Review, we focus specifically the role of PD-1/PD-L1 on Treg development and activity.

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Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

Cited by 44 publications

References 74 publications

The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats

The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats

Commensal bacterial modulation of the host immune response to ameliorate pain in a murine model of chronic prostatitis

Inhibitory Receptors and Pathways of Lymphocytes: The Role of PD-1 in Treg Development and Their Involvement in Autoimmunity Onset and Cancer Progression

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