Foxp3+ regulatory T cell therapy for tolerance in autoimmunity and solid organ transplantation

Sanders, Jes M.; Jeyamogan, Shareni; Mathew, James M.; Leventhal, Joseph R.

doi:10.3389/fimmu.2022.1055466

Cited by 13 publications

(15 citation statements)

References 193 publications

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“…Further, the induction of Tr1 cells could be a therapeutic lever that offers advantages over traditional FoxP3 + T reg therapies ( 40 ). While FoxP3 + T regs are essential for establishing tolerance ( 63 ), Tr1 cells have been identified as key players in sustaining this tolerance long-term ( 59 ). This understanding may reshape therapeutic strategies in SOT, with an emphasis on harnessing the unique properties of Tr1 cells to improve SOT outcomes.…”

Section: Cellular Therapeutic Strategies In Transplantation Patientsmentioning

confidence: 99%

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Knoedler,

Dean,

Diatta

et al. 2024

Front. Immunol.

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Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery.

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Section: Cellular Therapeutic Strategies In Transplantation Patientsmentioning

confidence: 99%

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Knoedler,

Dean,

Diatta

et al. 2024

Front. Immunol.

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“…A number of theories have been proposed in an attempt to explain the pathoetiology of classical autoimmune diseases, focusing on alterations in the B-cell antibody and cytokine production [22] and dysregulated suppressor cells, such as regulatory T cells (Treg) [23] and myeloid-derived suppressor cells (MDSC) [24]. Genetic risk factors predominantly include variants in MHC, immunoglobulins and T cell receptors, although not all susceptibility genes lead to an individual having an autoimmune disorder.…”

Section: Classical Autoimmunitymentioning

confidence: 99%

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Anderson¹,

Almulla

Reíter

et al. 2023

Cells

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Although previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8+ T cell and B-cell ‘autoimmune’-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8+ T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many ‘autoimmune’/‘immune-mediated’ disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies.

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“…Therefore, induction of M2 macrophages by Treg-derived exosomes may promote tumor growth. Immunosuppression of Tregs mainly inhibits the activation and proliferation of CD4 + and CD8 + T cells ( 60 ). Studies have shown that exosomes derived from Tregs suppress T-cell proliferation ( 61 , 62 ).…”

Section: T Cell-derived Exosomes In Tumor Immune Modulationmentioning

confidence: 99%

T cell-derived exosomes in tumor immune modulation and immunotherapy

et al. 2023

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Exosomes are nanoscale vesicles secreted by most cells and have a phospholipid bilayer structure. Exosomes contain DNA, small RNA, proteins, and other substances that can carry proteins and nucleic acids and participate in communication between cells. T cells are an indispensable part of adaptive immunity, and the functions of T cell-derived exosomes have been widely studied. In the more than three decades since the discovery of exosomes, several studies have revealed that T cell-derived exosomes play a novel role in cell-to-cell signaling, especially in the tumor immune response. In this review, we discuss the function of exosomes derived from different T cell subsets, explore applications in tumor immunotherapy, and consider the associated challenges.

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Foxp3+ regulatory T cell therapy for tolerance in autoimmunity and solid organ transplantation

Cited by 13 publications

References 193 publications

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

T cell-derived exosomes in tumor immune modulation and immunotherapy

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