A Bax‐dependent apoptosis pathway of CD4+CD25highFoxp3+ regulatory T cells is a new therapeutic target in regulation of immune responses

Abstract Myeloid antigen-presenting cells (APCs), regulatory cells, and the HLA-G molecule are involved in modulating immune responses and promoting tolerance. APCs are known to induce regulatory cells and to express HLA-G as well as 2 of its receptors; regulatory T cells can express and act through HLA-G; and HLA-G has been directly involved in the generation of regulatory cells. Thus, interplay(s) among HLA-G, APCs, and regulatory cells can be easily envisaged. However, despite a large body of evidence on the tolerogenic properties of HLA-G, APCs, and regulatory cells, little is known on how these tolerogenic players cooperate. In this review, we first focus on key aspects of the individual relationships between HLA-G, myeloid APCs, and regulatory cells. In its second part, we highlight recent work that gathers individual effects and demonstrates how intertwined the HLA-G/myeloid APCs/regulatory cell relationship is.

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Mesenchymal stem cells induce the expansion of regulatory T cells in abortion-prone mice

Reproduction ◽

10.1530/rep-20-0320 ◽

2021 ◽

Author(s):

Amir Salek Farrokhi ◽

Amir-Hassan Zarnani ◽

Fatemeh Rezaei kahmini ◽

Seyed Mohammad Moazzeni

Keyword(s):

Stem Cells ◽

T Cells ◽

Mesenchymal Stem Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Lymph Nodes ◽

De Novo ◽

Abortion Rate ◽

Cellular Mechanisms ◽

Inguinal Lymph Nodes

Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (i.p) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph nodes, and Ho1, Foxp3, Pd1, and Ctla4 genes expression at the feto-maternal interface were then measured on day 13.5 of pregnancy using flow cytometry and quantitative RT- PCR, respectively. The abortion rate in MSCs-treated mice was significantly reduced and normalized to the level observed in normal pregnant animals. We demonstrated a significant induction of Tregs in inguinal lymph nodes but not in the spleen following MSCs administration. Administration of MSCs remarkably upregulated the expression of HO1, Foxp3, Pd1, and Ctla4 genes in both placenta and decidua. Here, we show that MSCs therapy could protect the fetus in the abortion-prone mice through Tregs expansion and up-regulation of Treg-related genes. These events could establish an immune-privileged microenvironment, which participates in regulation of detrimental maternal immune responses against the semi-allogeneic fetus.

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Abstract A40: The balance between activated follicular helper T cells and follicular regulatory T cells within tertiary lymphoid structures guides antitumor immune responses in human breast cancer

10.1158/2326-6074.tumimm18-a40 ◽

2020 ◽

Author(s):

Grégory Noël ◽

Mireille Langouo ◽

Soizic Garaud ◽

Anaïs Boisson ◽

Hugues Duvillier ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Human Breast Cancer ◽

Helper T Cells ◽

Human Breast ◽

Follicular Helper ◽

Tertiary Lymphoid Structures ◽

Lymphoid Structures

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The Complex Role of Regulatory T Cells in Immunity and Aging

Frontiers in Immunology ◽

10.3389/fimmu.2020.616949 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lourdes Rocamora-Reverte ◽

Franz Leonard Melzer ◽

Reinhard Würzner ◽

Birgit Weinberger

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Immune Cells ◽

Treg Cells ◽

T Cell Subsets ◽

Γδt Cells ◽

Cell Functions ◽

Age Related ◽

Self Antigens

The immune system is a tightly regulated network which allows the development of defense mechanisms against foreign antigens and tolerance toward self-antigens. Regulatory T cells (Treg) contribute to immune homeostasis by maintaining unresponsiveness to self-antigens and suppressing exaggerated immune responses. Dysregulation of any of these processes can lead to serious consequences. Classically, Treg cell functions have been described in CD4+ T cells, but other immune cells also harbour the capacity to modulate immune responses. Regulatory functions have been described for different CD8+ T cell subsets, as well as other T cells such as γδT cells or NKT cells. In this review we describe the diverse populations of Treg cells and their role in different scenarios. Special attention is paid to the aging process, which is characterized by an altered composition of immune cells. Treg cells can contribute to the development of various age-related diseases but they are poorly characterized in aged individuals. The huge diversity of cells that display immune modulatory functions and the lack of universal markers to identify Treg make the expanding field of Treg research complex and challenging. There are still many open questions that need to be answered to solve the enigma of regulatory T cells.

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Targeting regulatory T cells for immunotherapy in melanoma

Molecular Biomedicine ◽

10.1186/s43556-021-00038-z ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Lili Huang ◽

Yeye Guo ◽

Shujing Liu ◽

Huaishan Wang ◽

Jinjin Zhu ◽

...

Keyword(s):

T Cells ◽

Tumor Microenvironment ◽

Regulatory T Cells ◽

Immune Responses ◽

Immune Cells ◽

Therapeutic Efficacy ◽

Patient Survival ◽

Therapeutic Antibodies ◽

Promising Strategy ◽

Fine Tune

AbstractRegulatory T cells (Tregs) are essential in the maintenance of immunity, and they are also a key to immune suppressive microenvironment in solid tumors. Many studies have revealed the biology of Tregs in various human pathologies. Here we review recent understandings of the immunophenotypes and suppressive functions of Tregs in melanoma, including Treg recruitment and expansion in a tumor. Tregs are frequently accumulated in melanoma and the ratio of CD8+ T cells versus Tregs in the melanoma is predictive for patient survival. Hence, depletion of Tregs is a promising strategy for the enhancement of anti-melanoma immunity. Many recent studies are aimed to target Tregs in melanoma. Distinguishing Tregs from other immune cells and understanding the function of different subsets of Tregs may contribute to better therapeutic efficacy. Depletion of functional Tregs from the tumor microenvironment has been tested to induce clinically relevant immune responses against melanomas. However, the lack of Treg specific therapeutic antibodies or Treg specific depleting strategies is a big hurdle that is yet to be overcome. Additional studies to fine-tune currently available therapies and more agents that specifically and selectively target tumor infiltrating Tregs in melanoma are urgently needed.

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Regulatory T cells in human geohelminth infection suppress immune responses to BCG andPlasmodium falciparum

European Journal of Immunology ◽

10.1002/eji.200939699 ◽

2010 ◽

Vol 40 (2) ◽

pp. 437-442 ◽

Cited By ~ 103

Author(s):

Linda J. Wammes ◽

Firdaus Hamid ◽

Aprilianto E. Wiria ◽

Brechje de Gier ◽

Erliyani Sartono ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Immune Responses

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2019 ATVB Plenary Lecture

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.312287 ◽

2020 ◽

Vol 40 (4) ◽

pp. 853-864 ◽

Cited By ~ 3

Author(s):

Tian X. Zhao ◽

Stephen A. Newland ◽

Ziad Mallat

Keyword(s):

Cardiovascular Disease ◽

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Interleukin 2 ◽

Cell Types ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Myocardial Repair

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.

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