Regulatory T cell function in autoimmune disease

Rajendeeran, Anandi; Tenbrock, Klaus

doi:10.1016/j.jtauto.2021.100130

Cited by 44 publications

(31 citation statements)

References 84 publications

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“…Other studies have shown a similar increase of Foxp3+ Tregs numbers in CeD, but found that the suppressive action of Tregs is reduced by local production of IL-15 42–44 . Increased numbers of Tregs are found in several inflammatory conditions in humans 45, 46 . However, their role in such conditions is still not clear.…”

Section: Discussionmentioning

confidence: 99%

The human small intestine contains two subsets of regulatory Foxp3+ CD4+ T cells with very different life span and functional properties

Chauhan

Bartolomé-Casado

Landsverk

et al. 2020

Preprint

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Gut resident regulatory CD4+ T (Tregs) cells in mice are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and the gut microbiota. In contrast, information about the phenotype and function of Tregs in the human gut is limited. Here, we performed a detailed characterization of Foxp3+ CD4 Tregs in human small intestine (SI). SI Foxp3+ CD4 T cells were CD45RA-CTLA4+CD127-and suppressed proliferation of autologous T cells. Approximately 60% of SI Tregs expressed the transcription factor Helios. When stimulated, Helios-Tregs produced IL-17, IFNγ and IL-10, whereas Helios+ Tregs produced very low levels of these cytokines.Sampling mucosal tissue from transplanted human duodenum we demonstrated that donor SI Helios+ Tregs have a rapid turnover rate whereas Helios-Tregs persisted for at least 1 yr post transplantation. In the normal SI, Foxp3+ Tregs constituted only 2% of all CD4 T cells, while in active celiac disease both subsets expanded 5-10-fold. Taken together, these findings suggest that human SI contains two phenotypically and functionally distinct Treg subsets (Helios+ and Helios-Tregs), which are reminiscent of rapidly renewed dietary antigen-specific Tregs and microbiota-specific Tregs resident in the mouse gut, respectively.

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Section: Discussionmentioning

confidence: 99%

The human small intestine contains two subsets of regulatory Foxp3+ CD4+ T cells with very different life span and functional properties

Chauhan

Bartolomé-Casado

Landsverk

et al. 2020

Preprint

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“…IL-2/STAT5 has an important role in the differentiation and homeostasis of Treg and CD8 + T cells that are the key effector cells of tumor immunity (B. J. Chen et al 2022;Frantz et al 2022;Kolios et al 2021;Rajendeeran and Tenbrock 2021). IL-2 promotes CD8 + T cell recognition and clearance of malignant cells for cancer immunotherapy in the early tumor stage, but sustained high levels of IL-2 in the tumor microenvironment induce CD8 + T cell depletion and dysfunction of T cells thus suppressing anti-tumor immunity (Y.…”

Section: Ism1 and Immunizationmentioning

confidence: 99%

Advances in research of biological functions of Isthmin-1

Yang

Qianhe

et al. 2023

J. Cell Commun. Signal.

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Isthmin-1 (ISM1) was initially thought to be a brain secretory factor, but with the development of technical means of research and the refinement of animal models, numerous studies have shown that this molecule is expressed in multiple tissues, suggesting that it may have multiple biological functions. As a factor that regulates growth and development, ISM1 is expressed in different animals with spatial and temporal variability and can coordinate the normal development of multiple organs. Recent studies have found that under the dependence of a non-insulin pathway, ISM1 can lower blood glucose, inhibit insulin-regulated lipid synthesis, promote protein synthesis, and affect the body's glucolipid and protein metabolism. In addition, ISM1 plays an important role in cancer development by promoting apoptosis and anti-angiogenesis, and by regulating multiple inflammatory pathways to influence the body's immune response. The purpose of this paper is to summarize relevant research results from recent years and to describe the key features of the biological functions of ISM1. We aimed to provide a theoretical basis for the study of ISM1 related diseases, and potential therapeutic strategies. Graphical abstract The main biological functions of ISM1. Current studies on the biological functions of ISM1 focus on growth and development, metabolism, and anticancer treatment. During embryonic development, ISM1 is dynamically expressed in the zebrafish, African clawed frog, chick, mouse, and human, is associated with craniofacial malformations, abnormal heart localization, and hematopoietic dysfunction. ISM1 plays an important role in regulating glucose metabolism, lipid metabolism, and protein metabolism in the body. ISM1 affects cancer development by regulating cellular autophagy, angiogenesis, and the immune microenvironment.

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“…An imbalance in the homeostasis of the immune system often leads to diseases 34 . A low number or weakened function of Tregs may lead to an overreaction of the immune system and therefore causes autoimmune diseases, such as immunodysregulation polyendocrinopathy enteropathy X‐linked syndrome (IPEX) 35‐37 . However, the excessive number or abnormal activation of Tregs can inhibit the immune response, and when this occurs to the tumor, the anti‐tumor immunity is impaired 38,39 .…”

Section: Role Of Cd25 In Cancermentioning

confidence: 99%

“…34 A low number or weakened function of Tregs may lead to an overreaction of the immune system and therefore causes autoimmune diseases, such as immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX). [35][36][37] However, the excessive number or abnormal activation of Tregs can inhibit the immune response, and when this occurs to the tumor, the anti-tumor immunity is impaired. 38,39 If the ratio of Teff/Treg cells is high, the over-activation of Teff cells or over-reduction of Treg cells will result in autoimmune disorders.…”

Section: Cd25 and Tregsmentioning

confidence: 99%

CD25: A potential tumor therapeutic target

Peng

Tao

Zhang

et al. 2022

Intl Journal of Cancer

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CD25 is the alpha‐chain of the heterotrimer IL‐2 receptor. CD25 is expressed on the surface of both immune and non‐immune cells with different frequencies. For cancers, CD25 is expressed at high levels in many types of hematological malignancies, but at low levels in most solid tumors. CD25 is also highly expressed in activated circulating immune cells and regulatory T cells (Tregs). Infiltration of Tregs in the tumor microenvironment can lead to an imbalanced ratio of effector T cells (Teffs) and Tregs, which is associated with the progression of cancers. A rescued Teff/Treg cell ratio indicates an efficient anti‐tumor response to immunotherapy. CD25 as a potential target for the depletion of Tregs is critical in developing new immunotherapeutic strategies. Few articles have summarized the relationships between CD25 and tumors, or the recent progress of drugs targeting CD25. In this paper, we will discuss the structures of IL‐2 and IL‐2R, the biological function of CD25 and its important role in tumor therapy. In addition, the latest research on drugs targeting CD25 has been summarized, providing guidance for future drug development.

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Regulatory T cell function in autoimmune disease

Cited by 44 publications

References 84 publications

The human small intestine contains two subsets of regulatory Foxp3+ CD4+ T cells with very different life span and functional properties

The human small intestine contains two subsets of regulatory Foxp3+ CD4+ T cells with very different life span and functional properties

Advances in research of biological functions of Isthmin-1

CD25: A potential tumor therapeutic target

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