scholarly journals TIGIT-Fc Promote Immune Tolerance at the Feto-maternal Interface

2019 ◽  
Author(s):  
Wenyan Fu ◽  
Zetong Ma ◽  
Changhai Lei ◽  
Min Ding ◽  
Shi Hu
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Tolerance ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Interleukin 10 ◽  
Immunological Tolerance ◽  
Direct Role ◽  
Tolerogenic Dendritic Cells ◽  
Pregnant Mice

AbstractThe perfect synchronization of maternal immune-endocrine mechanisms and those of the foetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-foetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. The treatment with TIGIT-Fc of human decidual dendritic cells (dDCs) increased the production of interleukin 10 and induced the dDCs to powerfully polarize the decidual CD4+ T cells towards a classic TH2 phenotype. The administration of TIGIT-Fc to CBA/J pregnant mice at preimplantation induced CD4+ forkhead box P3+ (Foxp3+) regulatory T cells and tolerogenic dendritic cells and increased pregnancy rates in a mouse model of abortive stress. Moreover, we proposed that progesterone play a direct role in the transcriptional regulation of the TIGIT gene in decidual immune cell subsets. The results suggested the therapeutic potential of the TIGIT-Fc fusion protein in reinstating immune tolerance in failing pregnancies.

scholarly journals TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenyan Fu ◽  
Renfei Cai ◽  
Zetong Ma ◽  
Tian Li ◽  
Changhai Lei ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Interleukin 10 ◽  
Immunological Tolerance ◽  
Tolerogenic Dendritic Cells ◽  
Immune Cell Subsets ◽  
Pregnant Mice ◽  
Antigen Presenting

The perfect synchronization of maternal immune-endocrine mechanisms and those of the fetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-fetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. The treatment with TIGIT-Fc of human decidual antigen presenting cells (APCs), the decidual dendritic cells (dDCs), and decidual macrophages (dMϕs) increased the production of interleukin 10 and induced the decidua APCs to powerfully polarize the decidual CD4+ T cells toward a classic TH2 phenotype. We further proposed that Notch signaling shows a pivotal effect on the transcriptional regulation in decidual immune cell subsets. Moreover, the administration of TIGIT-Fc to CBA/J pregnant mice at preimplantation induced CD4+ forkhead box P3+ (Foxp3+) regulatory T cells and tolerogenic dendritic cells and increased pregnancy rates in an abortion-prone animal model stress. The results suggested the therapeutic potential of the TIGIT-Fc fusion protein in reinstating immune tolerance in failing pregnancies.

scholarly journals Immunomodulatory Role and Therapeutic Potential of Non-Coding RNAs Mediated by Dendritic Cells in Autoimmune and Immune Tolerance-Related Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifeng Liu ◽  
Xiaoze Wang ◽  
Fan Yang ◽  
Yanyi Zheng ◽  
Tinghong Ye ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Autoimmune Diseases ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
The Body ◽  
Cytokines And Chemokines ◽  
Non Coding Rnas ◽  
And Function ◽  
Antigen Presenting

Dendritic cells (DCs) are professional antigen-presenting cells that act as a bridge between innate immunity and adaptive immunity. After activation, DCs differentiate into subtypes with different functions, at which point they upregulate co-stimulatory molecules and produce various cytokines and chemokines. Activated DCs also process antigens for presentation to T cells and regulate the differentiation and function of T cells to modulate the immune state of the body. Non-coding RNAs, RNA transcripts that are unable to encode proteins, not only participate in the pathological mechanisms of autoimmune-related diseases but also regulate the function of immune cells in these diseases. Accumulating evidence suggests that dysregulation of non-coding RNAs contributes to DC differentiation, functions, and so on, consequently producing effects in various autoimmune diseases. In this review, we summarize the main non-coding RNAs (miRNAs, lncRNAs, circRNAs) that regulate DCs in pathological mechanisms and have tremendous potential to give rise to novel therapeutic targets and strategies for multiple autoimmune diseases and immune tolerance-related diseases.

scholarly journals Vitamin D3-Induced Tolerogenic Dendritic Cells Modulate the Transcriptomic Profile of T CD4+ Cells Towards a Functional Hyporesponsiveness

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Navarro-Barriuso ◽  
María José Mansilla ◽  
Bibiana Quirant-Sánchez ◽  
Aina Teniente-Serra ◽  
Cristina Ramo-Tello ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Vitamin D3 ◽  
Therapeutic Potential ◽  
Promising Alternative ◽  
Transcriptomic Profile ◽  
Tolerogenic Dendritic Cells ◽  
Potential Biomarker ◽  
Relative Prevalence ◽  
Regulatory Properties

The use of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases. Among the different strategies available, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most robust approaches due to their immune regulatory properties, which are currently being tested in clinical trials. However, the mechanisms that vitD3-tolDC trigger for the induction of tolerance remain elusive. For this reason, we performed a full phenotypical, functional, and transcriptomic characterization of T cells upon their interaction with autologous, antigen-specific vitD3-tolDC. We observed a strong antigen-specific reduction of T cell proliferation, combined with a decrease in the relative prevalence of TH1 subpopulations and IFN-γ production. The analysis of the transcriptomic profile of T CD4+ cells evidenced a significant down-modulation of genes involved in cell cycle and cell response to mainly pro-inflammatory immune-related stimuli, highlighting the role of JUNB gene as a potential biomarker of these processes. Consequently, our results show the induction of a strong antigen-specific hyporesponsiveness combined with a reduction on the TH1 immune profile of T cells upon their interaction with vitD3-tolDC, which manifests the regulatory properties of these cells and, therefore, their therapeutic potential in the clinic.

scholarly journals STAT3 Activation in Combination with NF-KappaB Inhibition Induces Tolerogenic Dendritic Cells with High Therapeutic Potential to Attenuate Collagen-Induced Arthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Carolina Prado ◽  
Valentina Ugalde ◽  
Hugo González ◽  
Alicia Figueroa ◽  
Ernesto López ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Therapeutic Potential ◽  
Collagen Induced Arthritis ◽  
Tolerogenic Dendritic Cells ◽  
Nf Kappab ◽  
Stat3 Signalling ◽  
Inflammatory Phenotypes ◽  
Significant Therapeutic Effect ◽  
Constitutively Active

Dendritic cells (DCs) have the ability to induce tolerance or inflammation in response to self-antigens, which makes them fundamental players in autoimmunity. In this regard, immunogenic DCs produce IL-12 and IL-23 favouring the acquisition of Th1 and Th17 inflammatory phenotypes, respectively, by autoreactive CD4+ T-cells, thus promoting autoimmunity. Conversely, tolerogenic DCs produce IL-10 and TGF-β, inducing the generation of CD4+ T-cells with suppressive activity (Treg), which promote tolerance to self-constituents. Previous studies have shown that STAT3 signalling in DCs attenuates the production of proinflammatory cytokines, whilst NF-κB activation promotes it. In this study, we aimed to generate DCs displaying strong and constitutive tolerogenic profile to be used as immunotherapy in autoimmunity. To this end, we transduced bone marrow-derived DCs with lentiviral particles codifying for a constitutively active version of STAT3 (constitutively active STAT3 (STAT3ca)) or with a constitutive repressor of NF-κB (IκBα superrepressor (IκBαSR)), and their therapeutic potential was evaluated in a mouse model of arthritis induced by collagen (CIA). Our results show that STAT3ca transduction favoured the production of the anti-inflammatory mediator IL-10, whereas IκBαSR transduction attenuated the expression of the proinflammatory cytokine IL-23 in DCs. Moreover, both STAT3ca-transduced and IκBαSR-transduced DCs separately exerted a mild but significant therapeutic effect reducing the severity of CIA development. Furthermore, when DCs were transduced with both STAT3ca and IκBαSR together, they reduced CIA manifestation significantly stronger than when transduced with only STAT3ca or IκBαSR separately. These results show STAT3 and NF-κB as two important and complementary regulators of the tolerogenic behaviour of DCs, which should be considered as molecular targets in the design of DC-based suppressive immunotherapies for the treatment of autoimmune disorders.

Galectin-1 Confers Endometrial Gene Expression and Protein Related to Maternal-Conceptus Immune Tolerance in Cattle

2021 ◽  
Author(s):  
Heather L Chaney ◽  
Lindsay F Grose ◽  
Jeanna M LaBarbara ◽  
Adam W Sirk ◽  
Alyssa M Blancke ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
Estrous Cycle ◽  
Immune Tolerance ◽  
Immune Suppression ◽  
Carbohydrate Binding ◽  
Expression Of Genes ◽  
Pregnant Sheep ◽  
Carbohydrate Binding Proteins

Abstract Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic CD11c+ dendritic cells, increased anti-inflammatory IL-10, and activation of FOXP3+ regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-fetal immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3 and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7 and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10 and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3+ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.

Sign in / Sign up

Export Citation Format

Share Document