Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics

Skartsis, Nikolaos; Müller, Yannick D.; Ferreira, Leonardo M.R.

doi:10.1016/j.clim.2022.109201

Cited by 4 publications

(3 citation statements)

References 110 publications

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“…Tregs are vital for maintaining immune self-tolerance and regulation of immune tolerance by inhibiting autoimmune and inflammatory responses (8)(9)(10)(11). Natural CD4+ Tregs (nTregs) are derived from thymic precursors, consisting of approximately 5% to 10% of the circulating population of CD4+ T cells (12,13).…”

Section: Introductionmentioning

confidence: 99%

“…Natural Tregs-mediated immune regulation is mediated primarily by cell contact and suppressive cytokines ( Table 1A ). The immunoregulatory mechanism of nTregs includes the secretion of inhibitory cytokines with IL-10, IL35, TGF-β, and cell-contact inhibition with perforin and granzyme B, and the competition of IL-2 with effector T cell growth, and suppression of DC function ( 8 ). The tolerance of DCs can be induced by Tregs through positive feedback loops to reinforce the suppressive environment, and CTLA-4 expressed by Tregs can inhibit the expression of CD80 and CD86 on DCs to down-regulate effector T cells via the costimulatory cell surface protein CD28.…”

Section: Introductionmentioning

confidence: 99%

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Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Tsai,

Liao,

Hsiao

et al. 2023

Front. Immunol.

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Systemic lupus erythematosus (SLE) is a heterogeneous multisystem inflammatory disease with wide variability in clinical manifestations. Natural arising CD4+ regulatory T cells (Tregs) play a critical role in maintaining peripheral tolerance by suppressing inflammation and preventing autoimmune responses in SLE. Additionally, CD8+ regulatory T cells, type 1 regulatory T cells (Tr1), and B regulatory cells also have a less well-defined role in the pathogenesis of SLE. Elucidation of the roles of various Treg subsets dedicated to immune homeostasis will provide a novel therapeutic approach that governs immune tolerance for the remission of active lupus. Diminished interleukin (IL)-2 production is associated with a depleted Treg cell population, and its reversibility by IL-2 therapy provides important reasons for the treatment of lupus. This review focuses on the pathogenesis and new therapeutics of human Treg subsets and low-dose IL-2 therapy in clinical benefits with SLE.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Tsai,

Liao,

Hsiao

et al. 2023

Front. Immunol.

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“…Treg cells are a specialised subpopulation acting as suppressors of various immune responses [ 5 , 6 , 7 , 8 ]. It has been shown that Treg cells are able to inhibit immune cell functions, including T cell proliferation and cytokine production.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T Cells in Atherosclerosis: Is Adoptive Cell Therapy Possible?

Churov,

Chegodaev,

Khotina

et al. 2023

Life

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Atherosclerosis is an insidious vascular disease with an asymptomatic debut and development over decades. The aetiology and pathogenesis of atherosclerosis are not completely clear. However, chronic inflammation and autoimmune reactions play a significant role in the natural course of atherosclerosis. The pathogenesis of atherosclerosis involves damage to the intima, immune cell recruitment and infiltration of cells such as monocytes/macrophages, neutrophils, and lymphocytes into the inner layer of vessel walls, and the accumulation of lipids, leading to vascular inflammation. The recruited immune cells mainly have a pro-atherogenic effect, whereas CD4+ regulatory T (Treg) cells are another heterogeneous group of cells with opposite functions that suppress the pathogenic immune responses. Present in low numbers in atherosclerotic plaques, Tregs serve a protective role, maintaining immune homeostasis and tolerance by suppressing pro-inflammatory immune cell subsets. Compelling experimental data suggest that various Treg cell-based approaches may be important in the treatment of atherosclerosis. Here we highlight the most recent advances in our understanding of the roles of FOXP3-expressing CD4+ Treg cells in the atherogenic process and discuss potential translational strategies for the treatment of atherosclerosis by Treg manipulation.

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Classic costimulatory interactions in MAIT cell responses: from gene expression to immune regulation

Wang

Ninkov

Haeryfar

2023

Clinical and Experimental Immunology

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Summary Mucosa-associated invariant T (MAIT) cells are evolutionarily conserved, innate-like T lymphocytes with enormous immunomodulatory potentials. Due to their strategic localization, their invariant T cell receptor (iTCR) specificity for major histocompatibility complex-related protein 1 (MR1) ligands of commensal and pathogenic bacterial origin, and their sensitivity to infection-elicited cytokines, MAIT cells are best known for their antimicrobial characteristics. However, they are thought to also play important parts in the contexts of cancer, autoimmunity, vaccine-induced immunity, and tissue repair. While cognate MR1 ligands and cytokine cues govern MAIT cell maturation, polarization and peripheral activation, other signal transduction pathways, including those mediated by costimulatory interactions, regulate MAIT cell responses. Activated MAIT cells exhibit cytolytic activities and secrete potent inflammatory cytokines of their own, thus transregulating the biological behaviours of several other cell types, including dendritic cells, macrophages, natural killer cells, conventional T cells and B cells, with significant implications in health and disease. Therefore, an in-depth understanding of how costimulatory pathways control MAIT cell responses may introduce new targets for optimized MR1/MAIT cell-based interventions. Herein, we compare and contrast MAIT cells and mainstream T cells for their expression of classic costimulatory molecules belonging to the immunoglobulin superfamily and the tumour necrosis factor (TNF)/TNF receptor superfamily, based not only on the available literature but also on our transcriptomic analyses. We discuss how these molecules participate in MAIT cells’ development and activities. Finally, we introduce several pressing questions vis-à-vis MAIT cell costimulation and offer new directions for future research in this area.

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Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics

Cited by 4 publications

References 110 publications

Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Regulatory T Cells in Atherosclerosis: Is Adoptive Cell Therapy Possible?

Classic costimulatory interactions in MAIT cell responses: from gene expression to immune regulation

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