The transdifferentiation of regulatory T and Th17 cells in autoimmune/inflammatory diseases and its potential implications in pregnancy complications

2017 ◽  
Vol 78 (2) ◽  
pp. e12657 ◽  
Author(s):  
Zhao-Zhao Liu ◽  
Guo-Qiang Sun ◽  
Xiao-Hui Hu ◽  
Joanne Kwak-Kim ◽  
Ai-Hua Liao
Keyword(s):  
Pregnancy Complications ◽  
Th17 Cells ◽  
Inflammatory Diseases ◽  
In Pregnancy

scholarly journals Induction and stability of human Th17 cells require endogenous NOS2 and cGMP-dependent NO signaling

2013 ◽  
Vol 210 (7) ◽  
pp. 1433-1445 ◽  
Author(s):  
Nataša Obermajer ◽  
Jeffrey L. Wong ◽  
Robert P. Edwards ◽  
Kong Chen ◽  
Melanie Scott ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
De Novo ◽  
Inflammatory Diseases ◽  
Suppressor Cells ◽  
Guanosine Monophosphate ◽  
No Production ◽  
No Signaling

Nitric oxide (NO) is a ubiquitous mediator of inflammation and immunity, involved in the pathogenesis and control of infectious diseases, autoimmunity, and cancer. We observed that the expression of nitric oxide synthase-2 (NOS2/iNOS) positively correlates with Th17 responses in patients with ovarian cancer (OvCa). Although high concentrations of exogenous NO indiscriminately suppress the proliferation and differentiation of Th1, Th2, and Th17 cells, the physiological NO concentrations produced by patients’ myeloid-derived suppressor cells (MDSCs) support the development of RORγt(Rorc)+IL-23R+IL-17+ Th17 cells. Moreover, the development of Th17 cells from naive-, memory-, or tumor-infiltrating CD4+ T cells, driven by IL-1β/IL-6/IL-23/NO-producing MDSCs or by recombinant cytokines (IL-1β/IL-6/IL-23), is associated with the induction of endogenous NOS2 and NO production, and critically depends on NOS2 activity and the canonical cyclic guanosine monophosphate (cGMP)–cGMP-dependent protein kinase (cGK) pathway of NO signaling within CD4+ T cells. Inhibition of NOS2 or cGMP–cGK signaling abolishes the de novo induction of Th17 cells and selectively suppresses IL-17 production by established Th17 cells isolated from OvCa patients. Our data indicate that, apart from its previously recognized role as an effector mediator of Th17-associated inflammation, NO is also critically required for the induction and stability of human Th17 responses, providing new targets to manipulate Th17 responses in cancer, autoimmunity, and inflammatory diseases.

Ischaemic heart disease and pregnancy

Heart ◽  
2018 ◽  
Vol 105 (3) ◽  
pp. 189-195 ◽  
Author(s):  
Matthew Cauldwell ◽  
Lucia Baris ◽  
Jolien W Roos-Hesselink ◽  
Mark R Johnson
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Maternal Morbidity ◽  
Inflammatory Diseases ◽  
Later Life ◽  
Shock Delivery ◽  
Chronic Inflammatory Diseases ◽  
Prevalence Of Obesity ◽  
History Of ◽  
In Pregnancy

Although ischaemic heart disease is currently rarely encountered in pregnancy, occurring between 2.8 and 6.2 per 100 000 deliveries, it is becoming more common as women delay becoming pregnant until later life, when medical comorbidities are more common, and because of the higher prevalence of obesity in the pregnant population. In addition, chronic inflammatory diseases, which are more common in women, may contribute to greater rates of acute myocardial infarction (AMI). Pregnancy itself seems to be a risk factor for AMI, although the exact mechanisms are not clear. AMI in pregnancy should be investigated in the same manner as in the non-pregnant population, not allowing for delays, with investigations being conducted as they would outside of pregnancy. Maternal morbidity following AMI is high as a result of increased rates of heart failure, arrhythmia and cardiogenic shock. Delivery in women with history of AMI should be typically guided by obstetric indications not cardiac ones.

scholarly journals Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Functional Role ◽  
Inflammatory Diseases ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

scholarly journals Amino Terminal Recognition by a CCR6 Chemokine Receptor Antibody Blocks CCL20 Signaling and IL-17 Expression via β-arrestin

2021 ◽  
Author(s):  
Sara Gómez-Melero ◽  
Fé Isabel García-Maceira ◽  
Tania García-Maceira ◽  
Verónica Luna-Guerrero ◽  
Gracia Montero-Peñalvo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Chemokine Receptor ◽  
Th17 Cells ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Specific Binding ◽  
Isolation And Purification ◽  
Amino Terminal ◽  
Important Target

Abstract Background: CCR6 chemokine receptor is an important target in inflammatory diseases. Th17 cells express CCR6 and a number of inflammatory cytokines, including IL-17 and IL-22, which are involved in the propagation of inflammatory immune responses. CCR6 antagonist would be a potential treatment for inflammatory diseases such as psoriasis or rheumatoid arthritis. The aim of this study is to develop an antagonistic monoclonal antibody (mAb) against human CCR6 receptor (hCCR6).Results: We generate monoclonal antibodies against hCCR6 immunizing Balb/c mice with hCCR6 overexpressing cells. The antibodies were tested by flow cytometry for specific binding to hCCR6, cloned by limiting dilution and resulted in the isolation and purification monoclonal antibody 1C6. By ELISA and flow cytometry, was determined that the antibody obtained binds to hCCR6 N-terminal domain. The ability of 1C6 to neutralize hCCR6 signaling was tested and we determined that 1C6 antibody were able to block response in β-arrestin recruitment assay with IC50 10.23 nM, but did not inhibit calcium mobilization. In addition, we found in a chemotaxis assay that 1C6 reduces the migration of hCCR6 cells to their ligand CCL20. Finally, we determined by RT-qPCR that the expression of IL-17A in Th17 cells treated with 1C6 was inhibited.Conclusions: In the present study, we applied whole cell immunization for successfully obtain an antibody that is capable to neutralize hCCR6 signaling and to reduce hCCR6 cells migration and IL-17 expression. These results provide an efficient approach to obtain therapeutic potential antibodies in the treatment of CCR6-mediated inflammatory diseases.

scholarly journals Multivariate analysis of cytokine profiles in pregnancy complications

2018 ◽  
Vol 79 (3) ◽  
pp. e12818 ◽  
Author(s):  
Fawaz Azizieh ◽  
Kamaludin Dingle ◽  
Raj Raghupathy ◽  
Kjell Johnson ◽  
Jacob VanderPlas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Pregnancy Complications ◽  
Cytokine Profiles ◽  
In Pregnancy

Application of Nutraceuticals in Pregnancy Complications: Does Epigenetics Play a Role?

2017 ◽  
pp. 1-19
Author(s):  
Luís Fernando Schütz ◽  
Jomer Bernardo ◽  
Minh Le ◽  
Tincy Thomas ◽  
Chau Nguyen ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
In Pregnancy

scholarly journals When pregnancy tames the wolf

2019 ◽  
Vol 216 (5) ◽  
pp. 1012-1013
Author(s):  
Timothy B. Niewold ◽  
Shilpi Mehta-Lee
Keyword(s):  
Pregnancy Complications ◽  
Normal Pregnancy ◽  
Healthy Women ◽  
Transcriptional Modulation ◽  
In Pregnancy

A state of relative immunosuppression exists in normal pregnancy. In this issue of JEM, Hong et al. (https://doi.org/10.1084/jem.20190185) perform blood immunomonitoring in pregnancy, in both healthy women and women with lupus, and observe early and sustained transcriptional modulation of lupus-related pathways in both groups. When signatures of inflammation did not normalize in lupus, risk of pregnancy complications was increased.

scholarly journals A Novel Role for IL-6 Receptor Classic Signaling: Induction of RORγt+Foxp3+ Tregs with Enhanced Suppressive Capacity

2019 ◽  
Vol 30 (8) ◽  
pp. 1439-1453 ◽  
Author(s):  
Julia Hagenstein ◽  
Simon Melderis ◽  
Anna Nosko ◽  
Matthias T. Warkotsch ◽  
Johannes V. Richter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Th17 Cells ◽  
Inflammatory Diseases ◽  
Double Positive ◽  
T Effector Cells ◽  
Suppressive Capacity

BackgroundNew therapies blocking the IL-6 receptor (IL-6R) have recently become available and are successfully being used to treat inflammatory diseases like arthritis. Whether IL-6 blockers may help patients with kidney inflammation currently remains unknown.MethodsTo learn more about the complex role of CD4+ T cell-intrinsic IL-6R signaling, we induced nephrotoxic nephritis, a mouse model for crescentic GN, in mice lacking T cell–specific IL-6Ra. We used adoptive transfer experiments and studies in reporter mice to analyze immune responses and Treg subpopulations.ResultsLack of IL-6Ra signaling in mouse CD4+ T cells impaired the generation of proinflammatory Th17 cells, but surprisingly did not ameliorate the course of GN. In contrast, renal damage was significantly reduced by restricting IL-6Ra deficiency to T effector cells and excluding Tregs. Detailed studies of Tregs revealed unaltered IL-10 production despite IL-6Ra deficiency. However, in vivo and in vitro, IL-6Ra classic signaling induced RORγt+Foxp3+ double-positive Tregs (biTregs), which carry the trafficking receptor CCR6 and have potent immunoregulatory properties. Indeed, lack of IL-6Ra significantly reduced Treg in vitro suppressive capacity. Finally, adoptive transfer of T cells containing IL-6Ra−/− Tregs resulted in severe aggravation of GN in mice.ConclusionsOur data refine the old paradigm, that IL-6 enhances Th17 responses and suppresses Tregs. We here provide evidence that T cell–intrinsic IL-6Ra classic signaling indeed induces the generation of Th17 cells but at the same time highly immunosuppressive RORγt+ biTregs. These results advocate caution and indicate that IL-6–directed therapies for GN need to be cell-type specific.

scholarly journals Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases

2019 ◽  
Vol 20 (14) ◽  
pp. 3394 ◽  
Author(s):  
Kübra Bunte ◽  
Thomas Beikler
Keyword(s):  
Innate Immunity ◽  
Th17 Cells ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Th2 Cells ◽  
Immune Mediated ◽  
Bowel Diseases

Innate immunity represents the semi-specific first line of defense and provides the initial host response to tissue injury, trauma, and pathogens. Innate immunity activates the adaptive immunity, and both act highly regulated together to establish and maintain tissue homeostasis. Any dysregulation of this interaction can result in chronic inflammation and autoimmunity and is thought to be a major underlying cause in the initiation and progression of highly prevalent immune-mediated inflammatory diseases (IMIDs) such as psoriasis, rheumatoid arthritis, inflammatory bowel diseases among others, and periodontitis. Th1 and Th2 cells of the adaptive immune system are the major players in the pathogenesis of IMIDs. In addition, Th17 cells, their key cytokine IL-17, and IL-23 seem to play pivotal roles. This review aims to provide an overview of the current knowledge about the differentiation of Th17 cells and the role of the IL-17/IL-23 axis in the pathogenesis of IMIDs. Moreover, it aims to review the association of these IMIDs with periodontitis and briefly discusses the therapeutic potential of agents that modulate the IL-17/IL-23 axis.

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