Novel developments in the mechanisms of immune tolerance to allergens

Eiwegger, Thomas; Gruber, Saskia; Szépfalusi, Zsolt; Akdiş, Cezmi A.

doi:10.4161/hv.20903

Cited by 6 publications

(4 citation statements)

References 95 publications

(121 reference statements)

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“…In fourth place, within weeks to months, a dose-dependent increase in allergen-specific IgG4 is observed (58). These allergen-specific IgG4 antibodies are supposed to act as blocking antibodies interacting at the level of IgE-mediated effector cell activation (49,(59)(60)(61)(62). In particular, IL-10 produced by allergen-specific T regulatory cells and B regulatory cells has been linked to IgG4 (63).…”

Section: Time (Y)mentioning

confidence: 99%

“…Allergen-specific IgE increases within the first weeks to months of specific immunotherapy (2, 68) and decreases in many cases later on. The drop in specific IgE does not correlate with clinical improvement (69) and is not a suitable marker to be used for therapy monitoring or to evaluate SIT efficacy (49). This dissociation of events has been linked to long-living IgE-secreting plasma cells that survive in bone marrow and spleen (70).…”

Section: Time (Y)mentioning

confidence: 99%

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Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy.IgE-mediated food allergy represents the most important cause of anaphylaxis in childhood. While milk and egg allergy are associated with a high rate of natural tolerance development within the first 6 years of life, this is less clear for other food allergies. Consequently, once it is communicated the diagnosis persists often lifelong severely impacting the quality of life of the patient and the environment despite the recommendation to reconsider clinical tolerance development from time to time.Currently, avoidance, providing an emergency plan and teaching, is the standard of treatment; however, there is no cure or treatment that has reached the level of recommendation to re-induce tolerance to the symptom-eliciting food. Tolerance assessment occurs either via oral food challenges or due to unintended exposure. Given the cost and time intensiveness of oral food challenges and its potential harmfulness, there is eminent need to understand the process of tolerance development and define markers thereof to develop and monitor new treatment strategies for food allergy. This review aimed to provide an overview on recent advances regarding markers and mechanisms of tolerance development to food allergens.Oral tolerance in the context of food allergy is considered to occur if the antigen/food can be ingested without problems despite prolonged periods of avoidance, while the status of desensitization is strictly dependent on regular ingestion of the respective food in order to confer protection from allergic reactions. Currently, there is no general consensus on the exact time frame of avoidance and re-exposure that would allow the usage of the terminus tolerance that is considered equivalent to cure in the context of or...

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Section: Time (Y)mentioning

confidence: 99%

Section: Time (Y)mentioning

confidence: 99%

Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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“…It also suppresses the antigen-presenting capabilities to Th1 and Th2 of monocytes and APCs by down-regulating their expression of the class II major histocompatibility complex (MHC II) ( 95 ) and the co-stimulatory molecules CD54 (intercellular adhesion molecule-1, ICAM-1), CD80 and CD56 ( 96 – 99 ). Moreover, it can act on CD4+ T cells by inhibiting their antigen-specific activation and proliferation in lymph nodes, limiting their secretion of cytokines, such as IL-2, IFN-γ, IL-4, IL-5 and TNF-α, and their cytotoxic activity ( 45 , 100 , 101 ) and inducing their long-term anergy through the block of CD28 co-stimulatory signaling ( 102 , 103 ). Therefore, through these coordinated actions, IL-10 leads to the shutdown of the inflammatory immune response, both directly, by the suppression of macrophages and dendritic cells activity, and indirectly, by limiting T cells activation, differentiation and effector function and promoting peripheral tolerance ( 43 , 96 ).…”

Section: Il-10 Systemic Effectsmentioning

confidence: 99%

The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions

Carlini,

Noonan,

Abdalalem

et al. 2023

Front. Immunol.

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Interleukin-10 (IL-10) is a pleiotropic cytokine that has a fundamental role in modulating inflammation and in maintaining cell homeostasis. It primarily acts as an anti-inflammatory cytokine, protecting the body from an uncontrolled immune response, mostly through the Jak1/Tyk2 and STAT3 signaling pathway. On the other hand, IL-10 can also have immunostimulating functions under certain conditions. Given the pivotal role of IL-10 in immune modulation, this cytokine could have relevant implications in pathologies characterized by hyperinflammatory state, such as cancer, or infectious diseases as in the case of COVID-19 and Post-COVID-19 syndrome. Recent evidence proposed IL-10 as a predictor of severity and mortality for patients with acute or post-acute SARS-CoV-2 infection. In this context, IL-10 can act as an endogenous danger signal, released by tissues undergoing damage in an attempt to protect the organism from harmful hyperinflammation. Pharmacological strategies aimed to potentiate or restore IL-10 immunomodulatory action may represent novel promising avenues to counteract cytokine storm arising from hyperinflammation and effectively mitigate severe complications. Natural bioactive compounds, derived from terrestrial or marine photosynthetic organisms and able to increase IL-10 expression, could represent a useful prevention strategy to curb inflammation through IL-10 elevation and will be discussed here. However, the multifaceted nature of IL-10 has to be taken into account in the attempts to modulate its levels.

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“…59 . The involvement of acquired immunity and regulatory T-cells in allergy and in immnotherapy with allergens or anti-IgE moAbs, has been reviewed elsewhere, 56,[60][61][62][63] while a thorough role of basophils appears yet unclear. Immune tolerance induced by AIT should involve these mechanisms and dampen basophil response to allergen by a T-cell mediated mechanism.…”

mentioning

confidence: 99%

Immunotherapy in allergy and cellular tests

Chirumbolo

2014

Human Vaccines & Immunotherapeutics

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Novel developments in the mechanisms of immune tolerance to allergens

Cited by 6 publications

References 95 publications

Markers of tolerance development to food allergens

Markers of tolerance development to food allergens

The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions

Immunotherapy in allergy and cellular tests

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