scholarly journals 2019 ATVB Plenary Lecture

2020 ◽  
Vol 40 (4) ◽  
pp. 853-864 ◽  
Author(s):  
Tian X. Zhao ◽  
Stephen A. Newland ◽  
Ziad Mallat

Regulatory T cells and type-2 innate lymphoid cells represent 2 subsets of immune cells, which have been shown in preclinical models to be important in atherosclerosis and myocardial repair. Regulatory T cells play a crucial role in immune homeostasis and tolerance via their interactions with effector T cells, dendritic cells, and monocytes/macrophages. They also utilize and secrete inhibitory cytokines, including interleukin 10 and transforming growth factor β, to regulate or suppress pathogenic immune responses. Type-2 innate lymphoid cells have an important role in type-2 immune responses and tissue repair through secreting interleukins 5 and 13, as well as a variety of biological mediators and growth factors. Intriguingly, interleukin-2 has emerged as a common cytokine, which can be harnessed to upregulate both cell types, and also has important translational consequences as clinical trials are ongoing for its use in cardiovascular disease. Here, we briefly review the biology of these regulatory immune cell types, discuss the preclinical and clinical evidence for their functions in cardiovascular disease, examine the prospects for clinical translation and current ongoing trials, and finally, postulate how overlap in the mechanisms of upregulation may be leveraged in future treatments for patients.

2021 ◽  
Vol 12 ◽  
Author(s):  
Nhi Ngo Thi Phuong ◽  
Vittoria Palmieri ◽  
Alexandra Adamczyk ◽  
Robert Klopfleisch ◽  
Jost Langhorst ◽  
...  

The hallmarks of inflammatory bowel disease are mucosal damage and ulceration, which are known to be high-risk conditions for the development of colorectal cancer. Recently, interleukin (IL)-33 and its receptor ST2 have emerged as critical modulators in inflammatory disorders. Even though several studies highlight the IL-33/ST2 pathway as a key factor in colitis, a detailed mode of action remains elusive. Therefore, we investigated the role of IL-33 during intestinal inflammation and its potential as a novel therapeutic target in colitis. Interestingly, the expression of IL-33, but not its receptor ST2, was significantly increased in biopsies from the inflamed colon of IBD patients compared to non-inflamed colonic tissue. Accordingly, in a mouse model of Dextran Sulfate Sodium (DSS) induced colitis, the secretion of IL-33 significantly accelerated in the colon. Induction of DSS colitis in ST2-/- mice displayed an aggravated colon pathology, which suggested a favorable role of the IL 33/ST2 pathway during colitis. Indeed, injecting rmIL-33 into mice suffering from acute DSS colitis, strongly abrogated epithelial damage, pro-inflammatory cytokine secretion, and loss of barrier integrity, while it induced a strong increase of Th2 associated cytokines (IL-13/IL-5) in the colon. This effect was accompanied by the accumulation of regulatory T cells (Tregs) and type 2 innate lymphoid cells (ILC2s) in the colon. Depletion of Foxp3+ Tregs during IL-33 treatment in DSS colitis ameliorated the positive effect on the intestinal pathology. Finally, IL-33 expanded ILC2s, which were adoptively transferred to DSS treated mice, significantly reduced colonic inflammation compared to DSS control mice. In summary, our results emphasize that the IL-33/ST2 pathway plays a crucial protective role in colitis by modulating ILC2 and Treg numbers.


2015 ◽  
Vol 11 (2) ◽  
pp. e1004607 ◽  
Author(s):  
Anne-Gaelle Besnard ◽  
Rodrigo Guabiraba ◽  
Wanda Niedbala ◽  
Jennifer Palomo ◽  
Flora Reverchon ◽  
...  

2020 ◽  
Vol 145 ◽  
pp. 99-111 ◽  
Author(s):  
Xiaonan Gao ◽  
Jibin Lin ◽  
Yuqi Zheng ◽  
Shangwei Liu ◽  
Chengxing Liu ◽  
...  

2020 ◽  
Vol 220 ◽  
pp. 1-10
Author(s):  
Mohammad Ali-Hassanzadeh ◽  
Mahsa Sadat Hosseini ◽  
Moslem Ahmadi ◽  
Maryam Zare ◽  
Mojgan Akbarzadeh-Jahromi ◽  
...  

Stem Cells ◽  
2021 ◽  
Vol 39 (7) ◽  
pp. 975-987
Author(s):  
Xingliang Fan ◽  
Zhi-Bin Xu ◽  
Cheng-Lin Li ◽  
Hong-Yu Zhang ◽  
Ya-Qi Peng ◽  
...  

Nature ◽  
2019 ◽  
Vol 568 (7752) ◽  
pp. 405-409 ◽  
Author(s):  
Lei Zhou ◽  
Coco Chu ◽  
Fei Teng ◽  
Nicholas J. Bessman ◽  
Jeremy Goc ◽  
...  

2015 ◽  
Vol 17 (1) ◽  
pp. 76-86 ◽  
Author(s):  
Kazuyo Moro ◽  
Hiroki Kabata ◽  
Masanobu Tanabe ◽  
Satoshi Koga ◽  
Natsuki Takeno ◽  
...  

Blood ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 555-563 ◽  
Author(s):  
David J. Chung ◽  
Marco Rossi ◽  
Emanuela Romano ◽  
Jennifer Ghith ◽  
Jianda Yuan ◽  
...  

Abstract A comprehensive understanding of the complex, autologous cellular interactions and regulatory mechanisms that occur during normal dendritic cell (DC)–stimulated immune responses is critical to optimizing DC-based immunotherapy. We have found that mature, immunogenic human monocyte-derived DCs (moDCs) up-regulate the immune-inhibitory enzyme, indoleamine 2,3-dioxygenase (IDO). Under stringent autologous culture conditions without exogenous cytokines, mature moDCs expand regulatory T cells (Tregs) by an IDO-dependent mechanism. The priming of resting T cells with autologous, IDO-expressing, mature moDCs results in up to 10-fold expansion of CD4+CD25brightFoxp3+CD127neg Tregs. Treg expansion requires moDC contact, CD80/CD86 ligation, and endogenous interleukin-2. Cytofluorographically sorted CD4+ CD25brightFoxp3+ Tregs inhibit as much as 80% to 90% of DC-stimulated autologous and allogeneic T-cell proliferation, in a dose-dependent manner at Treg:T-cell ratios of 1:1, 1:5, and as low as 1:25. CD4+CD25brightFoxp3+ Tregs also suppress the generation of cytotoxic T lymphocytes specific for the Wilms tumor antigen 1, resulting in more than an 80% decrease in specific target cell lysis. Suppression by Tregs is both contact-dependent and transforming growth factor-β–mediated. Although mature moDCs can generate Tregs by this IDO-dependent mechanism to limit otherwise unrestrained immune responses, inhibition of this counter-regulatory pathway should also prove useful in sustaining responses stimulated by DC-based immunotherapy.


2016 ◽  
Vol 9 (6) ◽  
pp. 1384-1394 ◽  
Author(s):  
T Mchedlidze ◽  
M Kindermann ◽  
A T Neves ◽  
D Voehringer ◽  
M F Neurath ◽  
...  

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