The Next Frontier of Regulatory T Cells: Promising Immunotherapy for Autoimmune Diseases and Organ Transplantations

Terry, Lauren V.; Oo, Ye Htun

doi:10.3389/fimmu.2020.565518

Cited by 36 publications

(33 citation statements)

References 116 publications

(133 reference statements)

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“…Successful treatment of hepatic autoimmunity reduces hepatic inflammation and fibrosis. Our increased understanding of disease pathogenesis over the past few years suggests that a reduction in the dose and duration of steroid treatment can be considered, to minimize adverse effects associated with immunosuppression (41)(42)(43).…”

Section: Targeting Enclysis In Autoimmune Liver Diseasementioning

confidence: 99%

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

et al. 2021

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Persistent liver inflammation can lead to cirrhosis, which associates with significant morbidity and mortality worldwide. There are no curative treatments beyond transplantation, followed by long-term immunosuppression. The global burden of end stage liver disease has been increasing and there is a shortage of donor organs, therefore new therapies are desperately needed. Harnessing the power of the immune system has shown promise in certain autoimmunity and cancer settings. In the context of the liver, regulatory T cell (Treg) therapies are in development. The hypothesis is that these specialized lymphocytes that dampen inflammation may reduce liver injury in patients with chronic, progressive diseases, and promote transplant tolerance. Various strategies including intrinsic and extracorporeal expansion of Treg cells, aim to increase their abundance to suppress immune responses. We recently discovered that hepatocytes engulf and delete Treg cells by enclysis. Herein, we propose that inhibition of enclysis may potentiate existing regulatory T cell therapeutic approaches in patients with autoimmune liver diseases and in patients receiving a transplant. Moreover, in settings where the abundance of Treg cells could hinder beneficial immunity, such us in chronic viral infection or liver cancer, enhancement of enclysis could result in transient, localized reduction of Treg cell numbers and tip the balance towards antiviral and anti-tumor immunity. We describe enclysis as is a natural process of liver immune regulation that lends itself to therapeutic targeting, particularly in combination with current Treg cell approaches.

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Section: Targeting Enclysis In Autoimmune Liver Diseasementioning

confidence: 99%

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

et al. 2021

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“…When HDAC9 expression is down-regulated, sphere formation in culture is compromised. An indication of a role of HDAC9 in promoting anchorage-independent growth, as observed for other class IIa HDACs [ 76 , 94 , 95 ]. HCC cells abruptly up-regulate HDAC9 mRNA in response to sulfatide a pro-metastatic sulfated glycolipid [ 96 ], further sustaining a role of HDAC9 in cancer onset and progression.…”

Section: Regulation Of Hdac9 Expression and Cancermentioning

confidence: 84%

“…Regulatory T (T reg ) lymphocytes are key factors for the maintenance of the peripheral self-tolerance. T reg cells development and function is under the supervision of the TF FOXP3 [ 76 ]. Hdac9 is required for the regulation of the Foxp3-dependent immunosuppression.…”

Section: Hdac9 Expression In Inflammation and In The Immune Responmentioning

confidence: 99%

Quis Custodiet Ipsos Custodes (Who Controls the Controllers)? Two Decades of Studies on HDAC9

Brancolini

Giorgio

Formisano

et al. 2021

Life

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Understanding how an epigenetic regulator drives different cellular responses can be a tricky task. Very often, their activities are modulated by large multiprotein complexes, the composition of which is context- and time-dependent. As a consequence, experiments aimed to unveil the functions of an epigenetic regulator can provide different outcomes and conclusions, depending on the circumstances. HDAC9 (histone deacetylase), an epigenetic regulator that influences different differentiating and adaptive responses, makes no exception. Since its discovery, different phenotypes and/or dysfunctions have been observed after the artificial manipulation of its expression. The cells and the microenvironment use multiple strategies to control and monitor HDAC9 activities. To date, some of the genes under HDAC9 control have been identified. However, the exact mechanisms through which HDAC9 can achieve all the different tasks so far described, remain mysterious. Whether it can assemble into different multiprotein complexes and how the cells modulate these complexes is not clearly defined. In summary, despite several cellular responses are known to be affected by HDAC9, many aspects of its network of interactions still remain to be defined.

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“…In terms of treatment, there are many feasible methods, such as traditional drug therapy ( Jiang et al, 2020 ), immunotherapy ( Terry and Oo, 2020 ). For example, the IL-6 inhibitor, tocilizumab was well applied for treatments of RA ( Tanaka et al, 2018 ).…”

Section: Overview Of Autoimmune Diseasesmentioning

confidence: 99%

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

et al. 2021

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Interleukin-38 (IL-38), a new cytokine of interleukin-1 family (IL-1F), is expressed in the human heart, kidney, skin, etc. Recently, new evidence indicated that IL-38 is involved in the process of different autoimmune diseases. Autoimmune diseases are a cluster of diseases accompanied with tissue damage caused by autoimmune reactions, including rheumatoid arthritis (RA), psoriasis, etc. This review summarized the links between IL-38 and autoimmune diseases, as well as the latest knowledge about the function and regulatory mechanism of IL-38 in autoimmune diseases. Especially, this review focused on the differentiation of immune cells and explore future prospects, such as the application of IL-38 in new technologies. Understanding the function of IL-38 is helpful to shed light on the progress of autoimmune diseases.

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The Next Frontier of Regulatory T Cells: Promising Immunotherapy for Autoimmune Diseases and Organ Transplantations

Cited by 36 publications

References 116 publications

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

Quis Custodiet Ipsos Custodes (Who Controls the Controllers)? Two Decades of Studies on HDAC9

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

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