The role of FOXP3+ regulatory T cells in human autoimmune and inflammatory diseases

Clinical & Experimental Immunology, Год журнала: 2019, Номер 197(1), С. 24 - 35

Опубликована: Март 4, 2019

Summary CD4+ regulatory T cells (Treg) expressing the forkhead box protein 3 (FOXP3) transcription factor (Tregs) are instrumental for prevention of autoimmune diseases. There is increasing evidence that human population highly heterogeneous in phenotype and function. Numerous studies conducted diseases have shown Treg impaired either their suppressive function, number, or both. However, contribution FOXP3+ subpopulations to development autoimmunity has not been delineated detail. Rare genetic disorders involve deficits function can be studied develop a global idea impact partial complete deficiency specific molecular mechanism involved In patients with reduced numbers (but no functional deficiency), expansion autologous could suitable therapeutic approach: infusion in-vitro expanded cells, interleukin (IL)-2/anti-IL-2 complex, biology-based therapies may unless deficit corrected vivo/in vitro. Finally, it critical consider appropriate stage at which administration cellular therapy most effective. We discuss conflicting data regarding whether more effectual preventing initiation autoimmunity, ameliorating disease progression curing itself.

Язык: Английский

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Treatment with rapamycin can restore regulatory T-cell function in IPEX patients

Journal of Allergy and Clinical Immunology, Год журнала: 2019, Номер 145(4), С. 1262 - 1271.e13

Опубликована: Дек. 23, 2019

Язык: Английский

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Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: a systematic review

Clinical & Experimental Immunology, Год журнала: 2021, Номер 205(1), С. 28 - 43

Опубликована: Март 31, 2021

Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological characteristics between these two similar conditions. A literature search was conducted in PubMed, Web Science Scopus databases included studies were systematically evaluated. Overall, 434 (222 CHAI 212 LATAIE) patients found 101 eligible studies. The mainly reported from North America western Europe, while LATAIE predominantly Asian countries. CHAI, positive familial history (P < 0·001) LATAIE, consanguineous parents more common. the rates granulomas 0·001), malignancies = atopy cutaneous disorders neurological 0·002) higher, commonly complicated life-threatening infections 0·002), pneumonia 0·006), ear, nose throat organomegaly 0·023), autoimmune enteropathy 0·038) growth failure 0·001). Normal subsets immunoglobulins except low serum levels CD9+ B cells (14·0 versus 38·4%, P natural killer (NK) (21 41·1%, immunoglobulin (Ig)G (46·9 0·291) IgA (54·5 44·7%, 0·076) majority patients, respectively. most frequent biological immunosuppressive agents prescribed for rituximab abatacept, Further investigations into best conditioning treatment regimens pre- post-transplantation required improve survival rate transplanted patients.

Язык: Английский

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Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 3, 2024

Abstract More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction these antibodies, and AChR antibody-positive MG (AChR MG) exhibit impaired Treg function reduced numbers. The gut microbiota their metabolites play a crucial role in maintaining differentiation function. However, whether Tregs correlate activity remains unknown. Here, we demonstrate that butyric acid-producing bacteria serum acid level MG. Butyrate supplementation effectively enhanced suppressive Mechanistically, butyrate activates autophagy by inhibiting the mammalian target rapamycin. Activation increased oxidative phosphorylation surface expression cytotoxic T-lymphocyte-associated protein 4 on cells, thereby promoting This observed effect was blocked using chloroquine, an inhibitor, suggesting vital butyrate-activated We propose derived has potential therapeutic efficacy against restoring Tregs.

Язык: Английский

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Immunotherapy in hepatocellular carcinoma: an overview of immune checkpoint inhibitors, drug resistance, and adverse effects

ONCOLOGIE, Год журнала: 2024, Номер 26(1), С. 9 - 25

Опубликована: Янв. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a concerning liver cancer with rising incidence and mortality rates worldwide. The effectiveness of traditional therapies in managing advanced HCC limited, necessitating the development new therapeutic strategies. Immune checkpoint inhibitors (ICIs) have emerged as promising strategy for management. By preventing tumor cells from evading immune surveillance through immunological checkpoints, ICIs can restore system’s ability to target eliminate tumors. While show promise enhancing response against malignancies, challenges such drug resistance adverse reactions hinder their efficacy. To address these challenges, developing individualized ICI treatment strategies critical. Combining targeted therapy immunotherapy holds potential comprehensive effects. Additionally, biomarker-based offer predicting guiding personalized patient care. Future research should explore emerging methods optimize immunotherapy. This review provides an overview HCC, demonstrating some success promoting response. However, remain important considerations that must be addressed. As tailored plans evolve, prospect expected grow, offering opportunities improved outcomes.

Язык: Английский

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The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 6, 2025

Human Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in CTLA4 is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance variable disease expressivity, suggesting the presence of modifiers that trigger onset severity. Various genetic non-genetic potential triggers have been analyzed CTLA-4 cohorts, however, none them revealed clear association to disease. Multiple HLA haplotypes positively or negatively associated various autoimmune diseases inborn errors immunity (IEI) due relevance MHC strength T cell responses. In this exploratory study, we investigated onset, severity clinical manifestations specific class I (A, B C) II (DRB1 DQB1) alleles forty-three individuals harboring CTLA4. Twenty-six out 43 recruited presented moderate severe symptoms whereas 17 were completely healthy. frequency analysis, odds ratio analysis linkage used. The principal statistical analyses showed no positive between genotypes We found risk associations HLA-DQB1*05:01 HLA-DRB1*01:02 respiratory tract involvement HLA-C*05:01 affection neurological system CTLA-4-insufficient patients. Additionally, protective HLA-DRB1*01:01 gastrointestinal symptoms. Even though, our findings suggest HLA-A, -B, -C, DRB1, DQB1 do not contribute insufficiency, certain HLA-alleles may influence manifestation advocate for further investigation as larger cohorts insufficiency.

Язык: Английский

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Exploring antigenic variation in autoimmune endocrinopathy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 28, 2025

Autoimmune disorders develop owing to a misdirected immune response against self-antigen. Genetic studies have revealed that numerous variants in genes encoding system proteins are associated with the development of autoimmunity. Indeed, many these genetic key receptors or transcription factors common pathogenesis several different autoimmune conditions. In contrast, proclivity autoimmunity any specific target organ tissue is under-researched. This has particular relevance endocrine conditions, where organ-specific involvement rule. polymorphisms targets responses been shown be predisposition diseases, including type 1 diabetes, thyroid disease and Addison’s disease. Mechanistically, variations leading decreased intrathymic expression, overexpression, localisation, alternative splicing post-translational modifications can interfere tolerance induction process. review will summarise ways certain endocrine-specific antigens (INS, TSHR, TPO, CYP21A2, PIT-1) may predispose

Язык: Английский

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Safety of Immune Checkpoint Inhibitors in Patients With Pre-Existing Inflammatory Bowel Disease and Microscopic Colitis

JCO Oncology Practice, Год журнала: 2020, Номер 16(9), С. e933 - e942

Опубликована: Май 13, 2020

PURPOSE: Enterocolitis is among the leading adverse events associated with immune checkpoint inhibitors (ICIs). There are limited retrospective data regarding safety of ICIs in patients inflammatory bowel disease (IBD; ulcerative colitis, Crohn’s disease) because they have been generally excluded from clinical trials testing ICIs. Furthermore, there no outcome available microscopic a cause chronic diarrhea. We aimed to study cancer pre-existing IBD or colitis. METHODS: retrospectively reviewed records treated at our institution who received least 1 dose either programmed cell death-1 (PD-1)/ PD-1 ligand inhibitor, cytotoxic T-lymphocyte-associated antigen 4 both between 2011 and 2018. identified RESULTS: Of 548 solid tumor an ICI, we 25 colitis (21 IBD; colitis). An enterocolitis flare occurred 7 (28%): 3 (75%) 21 (19%) IBD. All were systemic corticosteroids, 2 required anti–tumor necrosis factor agent, one anti-integrin agent colectomy for treatment refractory ICI therapy was discontinued all experienced flare. CONCLUSION: In cohort, exacerbation notable percentage majority discontinuation Although these suggest that IBD/microscopic may be ICIs, additional studies needed validate results.

Язык: Английский

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Recent advances in nanoparticles-based photothermal therapy synergizing with immune checkpoint blockade therapy

Materials & Design, Год журнала: 2022, Номер 217, С. 110656 - 110656

Опубликована: Апрель 14, 2022

Several breakthroughs have been achieved in anti-tumor immune checkpoint blockade (ICB) therapy the past decade. Despite considerable therapeutic effects, ICB is still limited by low benefit rates and severe systemic toxicity. Pre-clinical studies shown that photothermal (PTT) mediated nanoparticles (NPs) can counterbalance drawbacks of produce synergistic effects. NPs offer several advantages such as increased tumor-targeting ability, high drug-loading capacity satisfying biocompatibility. Therefore, combining NPs-based PTT achieve a better outcome against tumors, even prevent metastatic recurrence inducing memory. Here, we discussed current progress PTT, along with pre-clinical trials on PTT/ICB combinational therapy. The synthesis mechanisms different also summarized. Moreover, challenges, deficiencies future improvement this novel treatment modality analyzed.

Язык: Английский

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Recent progress in cancer immunotherapy: Overview of current status and challenges

Pathology - Research and Practice, Год журнала: 2022, Номер 241, С. 154241 - 154241

Опубликована: Ноя. 24, 2022

Язык: Английский

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