Regulatory T Cells and Human Disease

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 541 - 566

Published: Feb. 4, 2020

Naturally occurring CD4+ regulatory T cells (Tregs), which specifically express the transcription factor FoxP3 in nucleus and CD25 CTLA-4 on cell surface, are a functionally distinct subpopulation actively engaged maintenance of immunological self-tolerance homeostasis. Recent studies have facilitated our understanding cellular molecular basis their generation, function, phenotypic functional stability, adaptability. It is under investigation humans how or numerical Treg anomalies, whether genetically determined environmentally induced, contribute to diseases such as autoimmune diseases. Also being addressed Tregs can be targeted control physiological pathological immune responses, for example, by depleting them enhance tumor immunity expanding treat This review discusses current immunobiology normal disease states, with perspective realization Treg-targeting therapies clinic.

Language: Английский

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Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: July 17, 2020

Abstract Regulatory T cells (Tregs) characterized by the expression of master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective immunosurveillance tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot field. However, Tregs are also essential for maintenance tolerance body share many molecular signalling pathways with conventional cells, including cytotoxic primary mediators tumour immunity. Hence, inability to specifically target neutralize microenvironment without globally compromising self-tolerance poses significant challenge. Here, we review recent advances characterizing tumour-infiltrating focus on functional roles costimulatory inhibitory receptors Tregs, evaluate their potential as clinical targets, systematically summarize treatment strategies. Also, propose modalities integrate our increasing knowledge phenotype function rational design checkpoint inhibitor-based combination therapies. Finally, possible strategies that can be used develop Treg-targeted

Language: Английский

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Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(2), P. 201 - 218.e9

Published: Jan. 28, 2022

Language: Английский

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Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Jan. 31, 2019

Regulatory T cells (Tregs) are important for the induction and maintenance of peripheral tolerance therefore, they key in preventing excessive immune responses autoimmunity. In last decades, several reports have been focussed on understanding biology Tregs their mechanisms action. Preclinical studies demonstrated ability to delay/prevent graft rejection control autoimmune following adoptive transfer vivo. Due these promising results, extensively studied as a potential new tool prevention and/or treatment diseases. Currently, solid organ transplantation remains choice end-stage failure. However, chronic ensuing side effects immunosuppressants represent main limiting factors acceptance patient survival. Autoimmune disorders diseases caused by breakdown against self-antigens. This is triggered either numerical or functional Treg defect, resistance effector suppression. this scenario, patients receiving high doses immunosuppressant left susceptible life-threatening opportunistic infections increased risk malignancies. 10 years, few phase I clinical trials aiming investigate safety feasibility Treg-based therapy completed published, whilst an increasing numbers still ongoing. The first results showed II already enrolling. review, we describe our focussing primarily ontogenesis, action methods used clinic isolation expansion. Furthermore, will ongoing from with setting disorders. Finally, discuss strategies further improve success therapy.

Language: Английский

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Helper T cell differentiation

Cellular and Molecular Immunology, Journal Year: 2019, Volume and Issue: 16(7), P. 634 - 643

Published: March 12, 2019

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T cells in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 19, 2023

T cells are crucial for immune functions to maintain health and prevent disease. cell development occurs in a stepwise process the thymus mainly generates CD4

Language: Английский

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Extracellular vesicles as tools and targets in therapy for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 5, 2024

Abstract Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers ubiquitously released from cells under normal pathological conditions. Human serum is a rich source of these EVs, though their isolation proteins non-EV lipid particles poses challenges. These transport various cellular components such as proteins, mRNAs, miRNAs, DNA, lipids across distances, influencing numerous physiological events, including those within tumor microenvironment (TME). Their pivotal roles in communication make EVs promising candidates for therapeutic agents, drug delivery systems, disease biomarkers. Especially cancer diagnostics, EV detection can pave way early identification offers potential diagnostic Moreover, subtypes emerging targeted tools, highlighting clinical significance. The need non-invasive biomarkers to monitor biological processes purposes remains unfulfilled. Tapping unique composition could unlock advanced avenues future. In this review, we discuss detail conditions, cancers (encompassing head neck, lung, gastric, breast, hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune renal diseases, emphasizing advancements molecular diagnostics delivery.

Language: Английский

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CD4 T Helper Cell Subsets and Related Human Immunological Disorders

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8011 - 8011

Published: Oct. 28, 2020

The immune system plays a critical role in protecting hosts from the invasion of organisms. CD4 T cells, as key component system, are central orchestrating adaptive responses. After decades investigation, five major helper cell (Th) subsets have been identified: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular helper) cells. Th1 defined by expression lineage cytokine interferon (IFN)-γ master transcription factor T-bet, participate type 1 responses to intracellular pathogens such mycobacterial species viruses; Th2 cytokines interleukin (IL)-4/IL-5/IL-13 GAΤA3, 2 larger extracellular helminths; Th17 IL-17/IL-22 RORγt, 3 including some bacteria fungi; producing IL-21 expressing Bcl6, help B cells produce corresponding antibodies; whereas Foxp3-expressing unlike Th1/Th2/Th17/Tfh exerting their effector functions, regulate maintain homeostasis prevent immunopathology. Interestingly, innate lymphoid (ILCs) found mimic functions three (Th1, Th17) thus can also be divided into subsets: ILC1s, ILC2s, ILC3s. In this review, we will discuss differentiation each subset context ILCs human diseases associated with dysregulation these lymphocyte particularly caused monogenic mutations.

Language: Английский

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Hair follicle immune privilege and its collapse in alopecia areata

Experimental Dermatology, Journal Year: 2020, Volume and Issue: 29(8), P. 703 - 725

Published: July 18, 2020

Anagen stage hair follicles (HFs) exhibit "immune privilege (IP)" from the level of bulge downwards to bulb. Both passive and active IP mechanisms protect HFs physiologically undesired immune responses limit surveillance. is relative, not absolute, primarily based on absent, or greatly reduced, intra-follicular antigen presentation via MHC class I II molecules, along with prominent expression "no danger" signals like CD200 creation an immunoinhibitory signalling milieu generated by secretory activities HFs. Perifollicular mast cells, Tregs other immunocytes may also contribute HF maintenance in healthy human skin. Collapse anagen bulb essential prerequisite for development alopecia areata (AA). In AA, lesional are rapidly infiltrated NKG2D + T cells natural killer (NK) while perifollicular acquire a profoundly pro-inflammatory phenotype interact autoreactive CD8+ cells. Using animal models, significant functional evidence has accumulated that demonstrates dominance system AA pathogenesis. Purified CD8+T-cell NK cell populations alone, which secrete fγ, suffice induce phenotype, CD4+T-cells aggravate it, iNKT provide relative protection against development. While collapse be induced exogenous agents, inherent deficiencies might confer increased susceptibility some individuals. Thus, key goal effective management re-establishment IP, will superior disease relapse.

Language: Английский

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Inducing immune tolerance with dendritic cell-targeting nanomedicines

Nature Nanotechnology, Journal Year: 2020, Volume and Issue: 16(1), P. 37 - 46

Published: Dec. 21, 2020

Language: Английский

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