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.

Hypersensitivity Reactions and Anaphylaxis

2020 ◽  
Author(s):  
Kristopher K. Ford ◽  
Timothy M. Loftus ◽  
Joseph J. Moellman
Keyword(s):  
Mast Cells ◽  
Clinical Manifestations ◽  
Allergic Reactions ◽  
Hypersensitivity Reactions ◽  
Life Threatening ◽  
Vasopressor Agents ◽  
Ige Mediated ◽  
Criteria For Diagnosis ◽  
Key Words Allergy

Allergic reactions vary in intensity from mild rash or allergic rhinitis to devastating anaphylactic shock. Anaphylaxis, often underrecognized and undertreated, can be a life-threatening syndrome leading to multiorgan dysfunction. This review covers the etiology, pathophysiology, and treatment of severe allergic reactions and anaphylaxis. It is precipitated by exposure to particular allergens—commonly food, medications, insect stings, and environmental exposures—in a previously sensitized individual. Symptoms develop from an IgE-mediated immune response leading to degranulation of mast cells and basophils and the release of preformed mediators, lipid-derived metabolites, and inflammatory cytokines. First-line treatment for anaphylaxis involves epinephrine. Secondary treatments are antihistamines and corticosteroids. Further treatments for patients refractory to standard therapies involve vasopressor agents, nebulized albuterol, and glucagon. Frequency and duration of biphasic reactions are variable, limiting the development of consensus guidelines for monitoring of anaphylactic reactions. Figures show the immune activity and inflammatory pathways in allergic responses, mast cell degranulation, and a depiction of common organs involved and corresponding clinical manifestations. Tables list the criteria for diagnosis of anaphylaxis, classification of hypersensitivity reactions, common clinical manifestations, and etiology and mediators of anaphylaxis.  This review contains 4 highly rendered figures, 11 tables, and 43 references. Key words: allergy, anaphylaxis, antihistamine, corticosteroid, epinephrine, mast cells

scholarly journals Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy

Immunity ◽  
2015 ◽  
Vol 43 (4) ◽  
pp. 788-802 ◽  
Author(s):  
Chun-Yu Chen ◽  
Jee-Boong Lee ◽  
Bo Liu ◽  
Shoichiro Ohta ◽  
Pin-Yi Wang ◽  
...  
Keyword(s):  
Food Allergy ◽  
Mast Cells ◽  
Mucosal Mast Cells ◽  
Ige Mediated ◽  
Interleukin 9

scholarly journals Clinical manifestations of immunoglobulin E‐mediated food allergy, including pollen‐food allergy syndrome

2020 ◽  
Vol 2 (1) ◽  
pp. 22-25
Author(s):  
Pooja Varshney ◽  
Jacqueline A. Pongracic
Keyword(s):  
Food Allergy ◽  
Immunoglobulin E ◽  
Acute Infection ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Physical Exertion ◽  
Allergic Reactions ◽  
Cutaneous Manifestations ◽  
Ige Mediated ◽  
Inflammatory Drugs

Immunoglobulin E-(IgE) mediated food allergy affects people of all ages but does not have a consistent presentation and may result in various manifestations, even for an individual. The onset of symptoms is usually quite rapid, minutes to a few hours after consumption of the allergen, although exceptions exist. Cutaneous and gastrointestinal symptoms are the most common clinical manifestations; however, they are not present in all allergic reactions. Clinicians, particularly those in emergency care settings, need to be aware that the lack of cutaneous manifestations does not exclude the possibility of anaphylaxis. It is extremely unusual for food allergy reactions to present with isolated upper or lower respiratory symptoms, nor is chronic urticaria a manifestation of food allergy. Clinical manifestations of IgE-mediated food allergy range from mild to severe and, in rare cases, can be fatal. Mild, localized reactions, such as those that occur in pollen‐food allergy syndrome, occur in individuals with sensitization to pollens. A small proportion of patients with this syndrome develop anaphylaxis. Alcohol, medications (nonsteroidal anti-inflammatory drugs, antacids), physical exertion, increased body temperature, acute infection, and menstruation are factors that are known to augment the severity of food-induced allergic reactions.

scholarly journals Salt-inducible kinase (SIK) inhibition is protective in a mouse model of asthma

2021 ◽  
Author(s):  
Manuel van Gijsel-Bonnello ◽  
Nicola J Darling ◽  
Laura McDonald ◽  
Mairi Sime ◽  
Jonathan Clark ◽  
...  
Keyword(s):  
Mast Cells ◽  
Allergic Asthma ◽  
Immune Cells ◽  
Immune Cell ◽  
Immunoglobulin E ◽  
Therapeutic Potential ◽  
Lymphoid Cells ◽  
Immune Cell Infiltration ◽  
Pharmacokinetic Properties

Interleukin-13 (IL-13) and other Th2 cytokines are important regulators of airway hyper-responsiveness, immune cell infiltration and inflammation in allergic asthma, and are produced when immune cells, such as type 2 innate lymphoid cells (ILC2s) and mast cells are stimulated with IL-33. Here, we report that the IL-33-dependent secretion of IL-13 from ILC2s is prevented by inhibition of the salt-inducible kinases (SIKs), as we have shown previously in mast cells (Darling NJ et al., 2021, J. Biol. Chem. doi: 10.1016/j.jbc.2021.100428). We also report that a new SIK inhibitor with improved pharmacokinetic properties suppresses the recruitment of eosinophils to the lungs and serum immunoglobulin E (IgE) levels in the Alternaria alternata-induced model of allergic asthma. Our results suggest that drugs targeting SIK isoforms may have therapeutic potential for the treatment of asthma.

scholarly journals Food allergy and breast-feeding

2020 ◽  
Vol 2 (1) ◽  
pp. 99-103
Author(s):  
Jennifer Pier ◽  
Kirsi M. Järvinen
Keyword(s):  
Food Allergy ◽  
Breast Feeding ◽  
Immunoglobulin E ◽  
Gastrointestinal Symptoms ◽  
Allergic Reactions ◽  
Unique Challenge ◽  
Food Avoidance ◽  
Food Antigens ◽  
Ige Mediated ◽  
Breast Fed

Breast-feeding is currently recommended as the optimal source of nutrition for infants; however, it is known that some individuals can excrete enough food antigens in breast milk to result in allergic reactions in infants, especially those already highly sensitized. These reactions can include non‐immunoglobulin E (IgE) mediated reactions, such as atopic dermatitis or gastrointestinal symptoms, and IgE-mediated reactions, such as anaphylaxis, although rare. Food reactions in infants who are breast-fed is a unique challenge because identifying the culprit foods may be more difficult and special consideration must be taken in ensuring proper nutrition during periods of food avoidance for both the infant and mother. This article reviews what is currently known about food allergy in infants who are breast-fed as well as offers insights into a proposed evaluation.

scholarly journals Germ-free mice exhibit mast cells with impaired functionality and gut homing and do not develop food allergy

2018 ◽  
Author(s):  
Martin Schwarzer ◽  
Petra Hermanova ◽  
Dagmar Srutkova ◽  
Jaroslav Golias ◽  
Tomas Hudcovic ◽  
...  
Keyword(s):  
Food Allergy ◽  
Mast Cells ◽  
Specific Ige ◽  
Edema Formation ◽  
Germ Free ◽  
Mechanistic Insight ◽  
Mucosal Mast Cells ◽  
Ige Mediated ◽  
Low Levels ◽  
Insight Into

ABSTRACTBackgroundMucosal mast cells (MC) are key players in IgE-mediated food allergy (FA). The evidence on the interaction between gut microbiota, MC and susceptibility to FA is contradictory.ObjectiveWe tested the hypothesis that commensal bacteria are essential for MC migration to the gut and their maturation impacting the susceptibility to FA.MethodsThe development and severity of FA symptoms was studied in sensitized germ-free (GF), conventional (CV) and mice mono-colonized with L. plantarum WCFS1 or co-housed with CV mice. MC were phenotypically and functionally characterized.ResultsSystemic sensitization and oral challenge of GF mice with ovalbumin led to increased levels of specific IgE in serum compared to CV mice. Remarkably, despite the high levels of sensitization, GF mice did not develop diarrhea or anaphylactic hypothermia, common symptoms of FA. In the gut, GF mice expressed low levels of the MC tissue-homing markers CXCL1 and CXCL2 and harbored fewer MC which exhibited lower levels of MC protease-1 after challenge. Additionally, MC in GF mice were less mature as confirmed by flow-cytometry and reduced edema formation after injection of degranulation-provoking compound 48/80. Co-housing of GF mice with CV mice fully restored their susceptibility to develop FA. However, this did not occur when GF mice were mono-colonized with L. plantarum.ConclusionOur results demonstrate that microbiota-induced maturation and gut-homing of MC is a critical step for the development of symptoms of experimental FA. This new mechanistic insight into microbiota-MC-FA axis can be exploited in the prevention and treatment of FA in humans.

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.

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