Control of Regulatory T Cells by Co-signal Molecules

Wing, James B.; Tay, Christopher; Sakaguchi, Shimon

doi:10.1007/978-981-32-9717-3_7

Cited by 29 publications

(26 citation statements)

References 155 publications

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“…Another important point is the reduction of regulatory T cells CD4 + CD25 + Foxp3 + verified in these patients. These cells have a fundamental role in the negative regulation of inflammation, control of cell proliferation, and the effector function of several cells, which probably has contributed to the excessive inflammation observed in critically ill patients (153,190). It has been described that regulatory T cells play a central role in mitigating the immune response in several viral infections (191); reducing the number of these cells in patients with COVID-19 can lead to loss of regulatory functions and consequent cytokine storm.…”

Section: T Helper Cellsmentioning

confidence: 99%

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

et al. 2020

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Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs. The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.

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Section: T Helper Cellsmentioning

confidence: 99%

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

et al. 2020

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“…Another attracting target is represented by the tumor necrosis factor receptor OX40 (CD134) [108,109]; when activated by its ligand OX40L, OX40 is involved in T-cell signaling activation, promoting T-cell survival and enhancing the expression of several molecules such as Bcl-2 anti-apoptotic molecules, cytokines, cyclin A, and cytokine receptor [110]. Therefore, as OX40 may promote proliferation and survival of CD4+ and CD8+ T cells, immunostimulatory agonistic agents are currently under investigation in several solid malignancies [111].…”

Section: Ici Monotherapymentioning

confidence: 99%

Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma

Mollica

Rizzo

Montironi

et al. 2020

Cancers

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Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.

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“…It has two main cell subtypes, CD4 + Tregs and CD8 + Tregs. CD4 + Tregs play a dominant role in the maintenance of immunological self-tolerance by preventing immune and autoimmune responses against self-antigens [2]. The proportion of CD4 + Tregs increased in early pregnancy, peaked in mid-pregnancy, and decreased in late pregnancy [3].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, PD-1 + /CD8 + Tregs generated in a cardiac allograft model are localized to graft, produce both IFN-γ and IL-4, and inhibit CD4 effector responses [18]. GITR expression can be observed at a high level in human and murine CD4 + and CD8 + Tregs following the activ *Correspondence:sdwangwj@126.com †Yuanyuan Zhao, Ning Li and Hongchu Bao contributed equally to this work 2 Reproduction Medical Center, the affiliated Yantai Yuhuangding Hospital of Qingdao University, 20…”

Section: Introductionmentioning

confidence: 99%

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

Zhao

Bao

et al. 2020

Preprint

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Background: Regulatory T cells (Tregs) are critical immunomodulators during pregnancy by preventing maternal T-cell activation against fetal cells. However, how characteristics of maternal Tregs vary during pregnancy is still unclear. We analyzed the proportion and phenotypic characteristics of peripheral blood Tregs in normal pregnant women, women with recurrent pregnancy loss (RPL) or gestational diabetes mellitus (GDM), and non-pregnant women.Methods: We investigated the proportion of CD4+ Tregs, CD8+ Tregs and the expression of PD-1, GITR, HLA-G and CTLA-4 on them in the peripheral blood of normal pregnancies during 1st (n = 28), 2nd (n = 43), and 3rd trimester (n = 33); In addition, we evaluated pregnancies in the 1st trimester complicated by RPL (n = 21), in the 2nd (n = 17) and 3rd trimester (n = 28) complicated by GDM. Non-pregnant women (n = 57) were also investigated using flow cytometry.Results: During normal pregnancy, the proportion of CD4+ Tregs in all trimester and CD8+ Tregs in 2nd and 3rd trimester were higher(P ＜ 0.05，respectively) compared with non-pregnancy women. Moreover, the proportion of CD4+ Tregs was higher in 2nd trimester compared to 1st and 3rd trimester (P ＜ 0.01) while the proportion of CD8+ Tregs was higher in 3rd trimester compared to 1st and 2nd trimester (P ＜ 0.05). Compared to non-pregnant studies, the proportion of GITR+/CD8+ Tregs and HLA-G+/CD8+ Tregs in all trimester were higher(P ＜ 0.05, respectively). Moreover, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs and CTLA-4+/CD8+ Tregs in 3rd trimester were significantly higher compared to 1st, 2nd trimester and non-pregnant group(P ＜ 0.05, respectively).In RPL and GDM groups, the proportions of CD4+ Tregs in all trimesters were decreased while the proportions of CD8+ Tregs in all trimesters were increased compared to normal pregnant group (P ＜ 0.05，respectively).In RPL group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs and HLA-G+/CD4+ Tregs were decreased compared to 1st trimester normal pregnant group (P ＜ 0.05，respectively). In 2nd trimester GDM group, the proportion of HLA-G+/CD4+ Tregs were decreased compared to 2nd trimester normal pregnant group (P ＜ 0.05，respectively). In 3rd trimester GDM group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs, GITR+/CD8+ Tregs and HLA-G+/CD8+Tregs were decreased compared to 3rd trimester normal pregnant group (P ＜ 0.05, respectively).Conclusions: The proportion of CD4+ Tregs and CD8+ Tregs increased during pregnancy, the proportions and subsets of CD4+ Tregs decreased and those of CD8+ Tregs increased in pregnancies complicated by RPL and GDM, indicating that regulatory T cells play a role in pregnancy maintenance, and the abnormal expression of Tregs might be related to the complicated pregnancy.

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Control of Regulatory T Cells by Co-signal Molecules

Cited by 29 publications

References 155 publications

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

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