CD8+ Tregs ameliorate inflammatory reactions in a murine model of allergic rhinitis

Lin, Lin; Dai, Fei; Wei, Jinjin; Zheng, Chen

doi:10.1186/s13223-021-00577-8

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…On the other hand, TGF-β is critical for the development and differentiation of Treg [ 137 ]. The effect of TGF-β on immune tolerance was studied by Lin et al, who assessed the role of Treg cells in the context of AR [ 138 ]. Their study showed that the adoptive transfer of AR CD8 + Treg increased the levels of TGF-β in mice nasal lavage fluids, which was associated with a reduced number of sneezes and nasal rubbing incidents in the treated animals.…”

Section: Micro-immunotherapy and 2lalerg ® : The U...mentioning

confidence: 99%

How an Immune-Factor-Based Formulation of Micro-Immunotherapy Could Interfere with the Physiological Processes Involved in the Atopic March

Jacques¹,

Floris²

2023

IJMS

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Allergic diseases consist of improper inflammatory reactions to antigens and are currently an important healthcare concern, especially considering their increasing worldwide development in recent decades. The “atopic march” defines the paradigm of allergic diseases occurring in chronological order and displaying specific spatial manifestations, as they usually start as atopic dermatitis (AD) and food allergies during infancy and progressively evolve into allergic asthma (AA) and allergic rhinitis (AR) or rhino-conjunctivitis in childhood. Many immune cell subtypes and inflammatory factors are involved in these hypersensitivity reactions. In particular, the T helpers 2 (Th2) subset, through its cytokine signatures made of interleukins (ILs), such as IL-4, IL-5, IL-10, and IL-13, as well as mast cells and their related histamine pathways, contribute greatly to the perpetuation and evolution of the atopic march. By providing low doses (LD) and ultra-low doses (ULD) of ILs and immune factors to the body, micro-immunotherapy (MI) constitutes an interesting therapeutic strategy for the management of the atopic march and its symptoms. One of the aims of this review is to shed light on the current concept of the atopic march and the underlying immune reactions occurring during the IgE-mediated responses. Moreover, the different classes of traditional and innovative treatments employed in allergic diseases will also be discussed, with a special emphasis on the potential benefits of the MI medicine 2LALERG® formulation in this context.

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Section: Micro-immunotherapy and 2lalerg ® : The U...mentioning

confidence: 99%

How an Immune-Factor-Based Formulation of Micro-Immunotherapy Could Interfere with the Physiological Processes Involved in the Atopic March

Jacques¹,

Floris²

2023

IJMS

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“…Certain research has indicated that, under chronic stimulation or specific pathological conditions, such as chronic infections or cancer, CD8+ T cells may experience immune exhaustion, characterized by a gradual loss of function and activity in response to sustained stimuli (41). Regulatory CD8+ T cells have inhibitory effects during AR occurrences, impacting inflammatory responses (42)(43)(44). Though not primary participants in allergic reactions, CD8+ T cells may exhibit exhaustion in response to allergens.…”

Section: Discussionmentioning

confidence: 99%

Genetically predicted N-methylhydroxyproline levels mediate the association between naive CD8+ T cells and allergic rhinitis: a mediation Mendelian randomization study

Chen,

Suo,

et al. 2024

Front. Immunol.

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BackgroundAllergic rhinitis (AR), a prevalent chronic inflammatory condition triggered by immunoglobulin E (IgE), involves pivotal roles of immune and metabolic factors in its onset and progression. However, the intricacies and uncertainties in clinical research render current investigations into their interplay somewhat inadequate.ObjectiveTo elucidate the causal relationships between immune cells, metabolites, and AR, we conducted a mediation Mendelian randomization (MR) analysis.MethodsLeveraging comprehensive publicly accessible summary-level data from genome-wide association studies (GWAS), this study employed the two-sample MR research method to investigate causal relationships among 731 immune cell phenotypes, 1400 metabolite levels, and AR. Additionally, employing the mediation MR approach, the study analyzed potential mediated effect of metabolites in the relationships between immune cells and AR. Various sensitivity analysis methods were systematically employed to ensure the robustness of the results.ResultsFollowing false discovery rate (FDR) correction, we identified three immune cell phenotypes as protective factors for AR: Naive CD8br %CD8br (odds ratio (OR): 0.978, 95% CI = 0.966–0.990, P = 4.5×10–4), CD3 on CD39+ activated Treg (OR: 0.947, 95% CI = 0.923–0.972, P = 3×10–5), HVEM on CD45RA- CD4+ (OR: 0.967, 95% CI = 0.948–0.986, P = 4×10–5). Additionally, three metabolite levels were identified as risk factors for AR: N-methylhydroxyproline levels (OR: 1.219, 95% CI = 1.104–1.346, P = 9×10–5), N-acetylneuraminate levels (OR: 1.133, 95% CI = 1.061–1.211, P = 1.7×10–4), 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4) levels (OR: 1.058, 95% CI = 1.029–1.087, P = 5×10–5). Mediation MR analysis indicated a causal relationship between Naive CD8br %CD8br and N-methylhydroxyproline levels, acting as a protective factor (OR: 0.971, 95% CI = 0.950–0.992, P = 8.31×10–3). The mediated effect was -0.00574, accounting for 26.1% of the total effect, with a direct effect of -0.01626. Naive CD8+ T cells exert a protective effect on AR by reducing N-methylhydroxyproline levels.ConclusionOur study, delving into genetic information, has substantiated the intricate connection between immune cell phenotypes and metabolite levels with AR. This reveals a potential pathway to prevent the onset of AR, providing guiding directions for future clinical investigations.

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“…This population is poorly studied and is usually a heterogeneous group [70, 71]. Since CD8 + T cells bind to MHC-I, CD8 + regulatory T lymphocytes are more studied in transplantation mouse models in comparison to food allergy, however some studies report that CD8 + CD25 + Foxp3 + T cells can ameliorate inflammatory responses in allergic diseases [71, 72]. These TGF-ß expressing regulatory T cells are crucial for the induction and maintenance of oral tolerance together with CD4 + regulatory T cells [73].…”

Section: Discussionmentioning

confidence: 99%

Expansion of Antigen- Specific Memory Cells as a Potential Booster for Food Tolerance Induction

Silva¹,

Marmello²,

Bentes³

et al. 2023

Preprint

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Approximately 3% of children in Western countries are diagnosed with peanut allergy, a likely lifelong disease. The preferred treatment for food allergy is allergen avoidance. However, oral immunotherapy is an FDA-approved treatment to re-induce tolerance, still, not all patients respond as expected. Thus, the aim of this work is to evaluate whether the association of an antigen-specific tolerogenic (oral tolerance) bystander effect can ameliorate the recovery of inflamed intestinal mucosa. Adult male C57BL/6 mice were divided into five groups, four of which were submitted to an intestinal inflammation induction protocol to peanuts. After sensitization, experimental groups were orally challenged with either peanuts or a hybrid diet (peanuts + mouse chow). In a second stage, groups were sensitized, challenged with peanuts, and then received either peanuts, hybrid diet, or ovalbumin chow during the recovery period of the inflamed mucosa. Results showed no changes in diet intake and body weight. Polyisotypic anti-peanut IgG and IgG1 were significantly increased in the serum from animals in allergic groups. The group that received the hybrid diet showed an increase in CD4+CD25+Foxp3+ regulatory T cells, as well as in B220+CD3-CD27+ memory B cells. Histology of the duodenum showed a decrease in intraepithelial leukocytes in animals who received hybrid diet. Together, our results show that when the tolerogen is added to a diet containing the allergen, it can ameliorate the induction of local inflammation. Simultaneously offering the allergen with a tolerated food increased the mucosal recovery due to the expansion of previously induced memory cells.

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CD8+ Tregs ameliorate inflammatory reactions in a murine model of allergic rhinitis

Cited by 7 publications

References 34 publications

How an Immune-Factor-Based Formulation of Micro-Immunotherapy Could Interfere with the Physiological Processes Involved in the Atopic March

How an Immune-Factor-Based Formulation of Micro-Immunotherapy Could Interfere with the Physiological Processes Involved in the Atopic March

Genetically predicted N-methylhydroxyproline levels mediate the association between naive CD8+ T cells and allergic rhinitis: a mediation Mendelian randomization study

Expansion of Antigen- Specific Memory Cells as a Potential Booster for Food Tolerance Induction

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