scholarly journals IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy

2020 ◽  
Vol 11 ◽  
Author(s):  
Cynthia Kanagaratham ◽  
Yasmeen S. El Ansari ◽  
Owen L. Lewis ◽  
Hans C. Oettgen
Keyword(s):  
Food Allergy ◽  
Mast Cells ◽  
Clinical Manifestations ◽  
Food Allergies ◽  
Th2 Cells ◽  
Igg Antibodies ◽  
Type 2 Immunity ◽  
Sequential Administration ◽  
Specific Igg

Food allergy is a major health issue, affecting the lives of 8% of U.S. children and their families. There is an urgent need to identify the environmental and endogenous signals that induce and sustain allergic responses to ingested allergens. Acute reactions to foods are triggered by the activation of mast cells and basophils, both of which release inflammatory mediators that lead to a range of clinical manifestations, including gastrointestinal, cutaneous, and respiratory reactions as well as systemic anaphylaxis. Both of these innate effector cell types express the high affinity IgE receptor, FcϵRI, on their surface and are armed for adaptive antigen recognition by very-tightly bound IgE antibodies which, when cross-linked by polyvalent allergen, trigger degranulation. These cells also express inhibitory receptors, including the IgG Fc receptor, FcγRIIb, that suppress their IgE-mediated activation. Recent studies have shown that natural resolution of food allergies is associated with increasing food-specific IgG levels. Furthermore, oral immunotherapy, the sequential administration of incrementally increasing doses of food allergen, is accompanied by the strong induction of allergen-specific IgG antibodies in both human subjects and murine models. These can deliver inhibitory signals via FcγRIIb that block IgE-induced immediate food reactions. In addition to their role in mediating immediate hypersensitivity reactions, mast cells and basophils serve separate but critical functions as adjuvants for type 2 immunity in food allergy. Mast cells and basophils, activated by IgE, are key sources of IL-4 that tilts the immune balance away from tolerance and towards type 2 immunity by promoting the induction of Th2 cells along with the innate effectors of type 2 immunity, ILC2s, while suppressing the development of regulatory T cells and driving their subversion to a pathogenic pro-Th2 phenotype. This adjuvant effect of mast cells and basophils is suppressed when inhibitory signals are delivered by IgG antibodies signaling via FcγRIIb. This review summarizes current understanding of the immunoregulatory effects of mast cells and basophils and how these functions are modulated by IgE and IgG antibodies. Understanding these pathways could provide important insights into innovative strategies for preventing and/or reversing food allergy in patients.

scholarly journals Developing food allergy: a potential immunologic pathway linking skin barrier to gut

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2660 ◽  
Author(s):  
Yui-Hsi Wang
Keyword(s):  
Food Allergy ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Allergic Reactions ◽  
Mucosal Mast Cells ◽  
Life Threatening ◽  
Ige Mediated

Immunoglobulin E (IgE)-mediated food allergy is an adverse reaction to foods and is driven by uncontrolled type-2 immune responses. Current knowledge cannot explain why only some individuals among those with food allergy are prone to develop life-threatening anaphylaxis. It is increasingly evident that the immunologic mechanisms involved in developing IgE-mediated food allergy are far more complex than allergic sensitization. Clinical observations suggest that patients who develop severe allergic reactions to food are often sensitized through the skin in early infancy. Environmental insults trigger epidermal thymic stromal lymphopoietin and interleukin-33 (IL-33) production, which endows dendritic cells with the ability to induce CD4+TH2 cell-mediated allergic inflammation. Intestinal IL-25 propagates the allergic immune response by enhancing collaborative interactions between resident type-2 innate lymphoid cells and CD4+TH2 cells expanded by ingested antigens in the gastrointestinal tract. IL-4 signaling provided by CD4+TH2 cells induces emigrated mast cell progenitors to become multi-functional IL-9-producing mucosal mast cells, which then expand greatly after repeated food ingestions. Inflammatory cytokine IL-33 promotes the function and maturation of IL-9-producing mucosal mast cells, which amplify intestinal mastocytosis, resulting in increased clinical reactivity to ingested food allergens. These findings provide the plausible view that the combinatorial signals from atopic status, dietary allergen ingestions, and inflammatory cues may govern the perpetuation of allergic reactions from the skin to the gut and promote susceptibility to life-threatening anaphylaxis. Future in-depth studies of the molecular and cellular factors composing these stepwise pathways may facilitate the discovery of biomarkers and therapeutic targets for diagnosing, preventing, and treating food allergy.

scholarly journals Pathophysiological Roles of Neuro-Immune Interactions between Enteric Neurons and Mucosal Mast Cells in the Gut of Food Allergy Mice

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1586
Author(s):  
Tomoe Yashiro ◽  
Hanako Ogata ◽  
Syed Faisal Zaidi ◽  
Jaemin Lee ◽  
Shusaku Hayashi ◽  
...  
Keyword(s):  
Food Allergy ◽  
Mast Cells ◽  
Imaging System ◽  
Receptor Gene ◽  
Nerve Fibers ◽  
Enteric Neurons ◽  
Food Allergies ◽  
Adenosine A3 Receptor ◽  
Myenteric Neurons ◽  
Mucosal Mast Cells

Recently, the involvement of the nervous system in the pathology of allergic diseases has attracted increasing interest. However, the precise pathophysiological role of enteric neurons in food allergies has not been elucidated. We report the presence of functional high-affinity IgE receptors (FcεRIs) in enteric neurons. FcεRI immunoreactivities were observed in approximately 70% of cholinergic myenteric neurons from choline acetyltransferase-eGFP mice. Furthermore, stimulation by IgE-antigen elevated intracellular Ca2+ concentration in isolated myenteric neurons from normal mice, suggesting that FcεRIs are capable of activating myenteric neurons. Additionally, the morphological investigation revealed that the majority of mucosal mast cells were in close proximity to enteric nerve fibers in the colonic mucosa of food allergy mice. Next, using a newly developed coculture system of isolated myenteric neurons and mucosal-type bone-marrow-derived mast cells (mBMMCs) with a calcium imaging system, we demonstrated that the stimulation of isolated myenteric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the adenosine A3 receptor antagonist MRE 3008F20. Moreover, the expression of the adenosine A3 receptor gene was detected in mBMMCs. Therefore, in conclusion, it is suggested that, through interaction with mucosal mast cells, IgE-antigen-activated myenteric neurons play a pathological role in further exacerbating the pathology of food allergy.

scholarly journals Total serum IgE and parasite: specific IgG and IgA antibodies in human strongyloidiasis

1993 ◽  
Vol 35 (4) ◽  
pp. 361-365 ◽  
Author(s):  
Cláudio L. Rossi ◽  
Emilia E. H. Takahashi ◽  
Cláudia D. Partel ◽  
Lívia G.V.L. Teodoro ◽  
Luiz J. da Silva
Keyword(s):  
Elevated Serum ◽  
Clinical Manifestations ◽  
Case Series ◽  
Total Serum ◽  
Igg Antibodies ◽  
Serum Ige ◽  
Iga Antibodies ◽  
Specific Igg ◽  
Mean Concentration ◽  
Specific Igg Antibodies

Total serum IgE, and Strongyloides - specific IgG and IgA antibodies were studied in 27 patients with parasitologically proven strongyloidiasis. Clinical manifestations in this case series were investigated by a restrospective study of the patient's records. Total serum IgE levels were elevated (greater than 250 IU/ml) in 59% of the patients (mean concentration = 1364 IU/ml). Parasite - specific IgG and IgA antibodies were detected by ELISA in the serum of 23 (85.2%) and 21 (77.8%) patients, respectively. Elevated serum IgE and clinical manifestations were not useful indexes of the presence of strongyloidiasis. On the other hand, our results support the view that serologic tests, particularly ELISA for detecting Strongyloides - specific IgG antibodies, can be usefully exploited for diagnostic purposes in strongyloidiasis.

scholarly journals Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Simon Schreiber ◽  
Christoph M. Hammers ◽  
Achim J. Kaasch ◽  
Burkhart Schraven ◽  
Anne Dudeck ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Allergic Diseases ◽  
Building Blocks ◽  
Th2 Cells ◽  
Th Cells ◽  
Th2 Cell ◽  
Type 2 Immunity ◽  
Mediate Immunity

The function of T cells is critically dependent on their ability to generate metabolic building blocks to fulfil energy demands for proliferation and consecutive differentiation into various T helper (Th) cells. Th cells then have to adapt their metabolism to specific microenvironments within different organs during physiological and pathological immune responses. In this context, Th2 cells mediate immunity to parasites and are involved in the pathogenesis of allergic diseases including asthma, while CD8+ T cells and Th1 cells mediate immunity to viruses and tumors. Importantly, recent studies have investigated the metabolism of Th2 cells in more detail, while others have studied the influence of Th2 cell-mediated type 2 immunity on the tumor microenvironment (TME) and on tumor progression. We here review recent findings on the metabolism of Th2 cells and discuss how Th2 cells contribute to antitumor immunity. Combining the evidence from both types of studies, we provide here for the first time a perspective on how the energy metabolism of Th2 cells and the TME interact. Finally, we elaborate how a more detailed understanding of the unique metabolic interdependency between Th2 cells and the TME could reveal novel avenues for the development of immunotherapies in treating cancer.

Systematic evaluation of nine monogenic autoinflammatory diseases reveals common and disease-specific correlations with allergy-associated features

2021 ◽  
pp. annrheumdis-2020-219137
Author(s):  
Daniella Muallem Schwartz ◽  
Moses M Kitakule ◽  
Brian LP Dizon ◽  
Cristhian Gutierrez-Huerta ◽  
Sarah A Blackstone ◽  
...  
Keyword(s):  
High Rate ◽  
Autoinflammatory Diseases ◽  
Th2 Cells ◽  
Systematic Evaluation ◽  
Neutrophilic Dermatosis ◽  
Tumour Necrosis Factor Receptor ◽  
Periodic Syndrome ◽  
Clinical Phenotypes ◽  
Type 2 Immunity

BackgroundMonogenic autoinflammatory diseases (AID) are caused by mutations in innate immune genes. The effects of these mutations on allergic inflammation are unknown.ObjectivesWe investigated allergic, immunological and clinical phenotypes in FMF (familial Mediterranean fever), CAPS (cryopyrin-associated periodic syndrome), TRAPS (tumour necrosis factor receptor-associated periodic syndrome), HIDS (hyper-IgD syndrome), PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), DADA2 (deficiency of adenosine deaminase 2), HA20 (haploinsufficiency of A20), CANDLE (chronic atypical neutrophilic dermatosis, lipodystrophy, elevated temperature) and SAVI (STING-associated vasculopathy of infancy).MethodsIn this cross-sectional study, clinical data were assessed in 425 patients with AID using questionnaires and chart reviews. Comparator data were obtained from public databases. Peripheral blood mononuclear cells obtained from 55 patients were stimulated and CD4+ cytokine production assessed.ResultsClinical laboratory features of Type 2 immunity were elevated in CAPS but reduced in most AID, particularly DADA2. Physician-diagnosed allergic diseases were prevalent in multiple AID, including CAPS and DADA2. T helper 2 (Th2) cells were expanded in CAPS, TRAPS and HIDS; Th9 cells were expanded in HA20.ConclusionsCAPS is characterised by an enhanced Type 2 signature, whereas FMF and CANDLE are associated with reduced Type 2 responses. DADA2 is associated with reduced Type 2 responses but a high rate of physician-diagnosed allergy. Therefore, NLRP3-driven autoinflammation may promote Type 2 immunity, whereas AID like DADA2 may manifest clinical phenotypes that masquerade as allergic disorders. Further investigations are needed to determine the contribution of autoinflammation to allergic clinical and immunological phenotypes, to improve the treatment of patients with AID.

scholarly journals Regulation of type 2 immunity to helminths by mast cells

Gut Microbes ◽  
2012 ◽  
Vol 3 (5) ◽  
pp. 476-481 ◽  
Author(s):  
Matthew R. Hepworth ◽  
Marcus Maurer ◽  
Susanne Hartmann
Keyword(s):  
Mast Cells ◽  
Type 2 Immunity

scholarly journals The Absence of Interleukin 1 Receptor–Related T1/St2 Does Not Affect T Helper Cell Type 2 Development and Its Effector Function

1999 ◽  
Vol 190 (10) ◽  
pp. 1541-1548 ◽  
Author(s):  
Katsuaki Hoshino ◽  
Shin-ichiro Kashiwamura ◽  
Kozo Kuribayashi ◽  
Taku Kodama ◽  
Tohru Tsujimura ◽  
...  
Keyword(s):  
Mast Cells ◽  
Cell Function ◽  
Interleukin 1 ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Nippostrongylus Brasiliensis ◽  
T Helper ◽  
Th2 Responses ◽  
And Function

T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells. T1/ST2 is also expressed on mast cells, which are critical for Th2-mediated effector responses. To evaluate whether T1/ST2 is required for Th2 responses and mast cell function, we have generated T1/ST2-deficient (T1/ST2−/−) mice and examined the roles of T1/ST2. Naive CD4+ T cells isolated from T1/ST2−/− mice developed to Th2 cells in response to IL-4 in vitro. T1/ST2−/− mice showed normal Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis as well as in the mouse model of allergen-induced airway inflammation. In addition, differentiation and function of bone marrow–derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells.

scholarly journals Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system

2006 ◽  
Vol 203 (6) ◽  
pp. 1435-1446 ◽  
Author(s):  
David Voehringer ◽  
Tiffany A. Reese ◽  
Xiaozhu Huang ◽  
Kanade Shinkai ◽  
Richard M. Locksley
Keyword(s):  
Airway Hyperreactivity ◽  
Th2 Cells ◽  
Nippostrongylus Brasiliensis ◽  
Lung Pathology ◽  
Cell Recruitment ◽  
Th2 Cell ◽  
Type 2 Immunity ◽  
Tissue Responses ◽  
Worm Expulsion

Nippostrongylus brasiliensis infection and ovalbumin-induced allergic lung pathology are highly interleukin (IL)-4/IL-13 dependent, but the contributions of IL-4/IL-13 from adaptive (T helper [Th]2 cells) and innate (eosinophil, basophils, and mast cells) immune cells remain unknown. Although required for immunoglobulin (Ig)E induction, IL-4/IL-13 from Th2 cells was not required for worm expulsion, tissue inflammation, or airway hyperreactivity. In contrast, innate hematopoietic cell–derived IL-4/IL-13 was dispensable for Th2 cell differentiation in lymph nodes but required for effector cell recruitment and tissue responses. Eosinophils were not required for primary immune responses. Thus, components of type 2 immunity mediated by IL-4/IL-13 are partitioned between T cell–dependent IgE and an innate non-eosinophil tissue component, suggesting new strategies for interventions in allergic immunity.

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