scholarly journals Thermoneutrality Alters Gastrointestinal Antigen Passage Patterning and Predisposes to Oral Antigen Sensitization in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Taeko K. Noah ◽  
Jee-Boong Lee ◽  
Christopher A. Brown ◽  
Amnah Yamani ◽  
Sunil Tomar ◽  
...  
Keyword(s):  
Mast Cell ◽  
Food Allergy ◽  
Cell Activation ◽  
Oral Challenge ◽  
Mast Cell Activation ◽  
Oral Exposure ◽  
Standard Temperature ◽  
Cellular Patterning ◽  
The Impact ◽  
Egg Antigen

Food allergy is an emerging epidemic, and the underlying mechanisms are not well defined partly due to the lack of robust adjuvant free experimental models of dietary antigen sensitization. As housing mice at thermoneutrality (Tn) - the temperature of metabolic homeostasis (26–30°C) – has been shown to improve modeling various human diseases involved in inflammation, we tested the impact of Tn housing on an experimental model of food sensitization. Here we demonstrate that WT BALB/c mice housed under standard temperature (18–20°C, Ts) conditions translocated the luminal antigens in the small intestine (SI) across the epithelium via goblet cell antigen passages (GAPs). In contrast, food allergy sensitive Il4raF709 mice housed under standard temperature conditions translocated the luminal antigens in the SI across the epithelium via secretory antigen passages (SAPs). Activation of SI antigen passages and oral challenge of Il4raF709 mice with egg allergens at standard temperature predisposed Il4raF709 mice to develop an anaphylactic reaction. Housing Il4raF709 mice at Tn altered systemic type 2 cytokine, IL-4, and the landscape of SI antigen passage patterning (villus and crypt involvement). Activation of SI antigen passages and oral challenge of Il4raF709 mice with egg antigen under Tn conditions led to the robust induction of egg-specific IgE and development of food-induced mast cell activation and hypovolemic shock. Similarly, Tn housing of WT BALB/c mice altered the cellular patterning of SI antigen passage (GAPs to SAPs). Activation of SI antigen passages and the oral challenge of WT BALB/c mice with egg antigen led to systemic reactivity to egg and mast cell activation. Together these data demonstrate that Tn housing alters antigen passage cellular patterning and landscape, and concurrent oral exposure of egg antigens and SAP activation is sufficient to induce oral antigen sensitization.

scholarly journals IL-2-Agonist-Induced IFN-γ Exacerbates Systemic Anaphylaxis in Food Allergen-Sensitized Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Christopher W.M. Link ◽  
Christina N. Rau ◽  
Christopher C. Udoye ◽  
Mohab Ragab ◽  
Rabia Ü. Korkmaz ◽  
...  
Keyword(s):  
Mast Cell ◽  
Food Allergy ◽  
Cell Activation ◽  
Allergic Sensitization ◽  
Specific Ige ◽  
Mast Cell Activation ◽  
Food Allergies ◽  
Th1 Response ◽  
Ifn Γ ◽  
The Impact

Food allergies are common, costly and potentially life-threatening disorders. They are driven by Th2, but inhibited by Th1 reactions. There is also evidence indicating that IL-2 agonist treatment inhibits allergic sensitization through expansion of regulatory T cells. Here, we tested the impact of an IL-2 agonist in a novel model for food allergy to hen´s egg in mice sensitized without artificial adjuvants. Prophylactic IL-2 agonist treatment expanded Treg populations and inhibited allergen-specific sensitization. However, IL-2 agonist treatment of already sensitized mice increased mast cell responses and allergic anaphylaxis upon allergen re-challenge. These effects depended on allergen-specific IgE and were mediated through IFN-γ, as shown by IgE transfer and blockade of IFN-γ with monoclonal antibodies. These results suggest that although shifting the allergic reaction toward a Treg/Th1 response inhibits allergic sensitization, the prototypic Th1 cytokine IFN-γ promotes mast cell activation and allergen-induced anaphylaxis in individuals that are already IgE-sensitized. Hence, while a Th1 response can prevent the development of food allergy, IFN-γ has the ability to exacerbate already established food allergy.

scholarly journals Stress-Induced Mast Cell Activation in Glabrous and Hairy Skin

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Constantin Căruntu ◽  
Daniel Boda ◽  
Sorin Musat ◽  
Ana Căruntu ◽  
Eugen Mandache
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Prolonged Exposure ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Glabrous Skin ◽  
Stress Exposure ◽  
Hairy Skin ◽  
The Impact

Mast cells play a key role in modulation of stress-induced cutaneous inflammation. In this study we investigate the impact of repeated exposure to stress on mast cell degranulation, in both hairy and glabrous skin. Adult male Wistar rats were randomly divided into four groups: Stress 1 day(n=8), Stress 10 days(n=7), Stress 21 days(n=6), and Control(n=8). Rats in the stress groups were subjected to 2 h/day restraint stress. Subsequently, glabrous and hairy skin samples from animals of all groups were collected to assess mast cell degranulation by histochemistry and transmission electron microscopy. The impact of stress on mast cell degranulation was different depending on the type of skin and duration of stress exposure. Short-term stress exposure induced an amplification of mast cell degranulation in hairy skin that was maintained after prolonged exposure to stress. In glabrous skin, even though acute stress exposure had a profound stimulating effect on mast cell degranulation, it diminished progressively with long-term exposure to stress. The results of our study reinforce the view that mast cells are active players in modulating skin responses to stress and contribute to further understanding of pathophysiological mechanisms involved in stress-induced initiation or exacerbation of cutaneous inflammatory processes.

scholarly journals Spontaneous food allergy inWas−/−mice occurs independent of FcεRI-mediated mast cell activation

Allergy ◽  
2017 ◽  
Vol 72 (12) ◽  
pp. 1916-1924 ◽  
Author(s):  
W. S. Lexmond ◽  
J. A. Goettel ◽  
B. F. Sallis ◽  
K. McCann ◽  
E. H. H. M. Rings ◽  
...  
Keyword(s):  
Mast Cell ◽  
Food Allergy ◽  
Cell Activation ◽  
Mast Cell Activation

scholarly journals Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy

2020 ◽  
Vol 11 ◽  
Author(s):  
Dylan Krajewski ◽  
Stephanie H. Polukort ◽  
Justine Gelzinis ◽  
Jeffrey Rovatti ◽  
Edwin Kaczenski ◽  
...  
Keyword(s):  
Mast Cell ◽  
Food Allergy ◽  
Mast Cells ◽  
Cell Activation ◽  
Cell Activity ◽  
Mast Cell Activation ◽  
Protective Effects ◽  
Ige Mediated ◽  
Protein Disulfide

The thiol isomerase, protein disulfide isomerase (PDI), plays important intracellular roles during protein folding, maintaining cellular function and viability. Recent studies suggest novel roles for extracellular cell surface PDI in enhancing cellular activation and promoting their function. Moreover, a number of food-derived substances have been shown to regulate cellular PDI activity and alter disease progression. We hypothesized that PDI may have similar roles during mast cell-mediated allergic responses and examined its effects on IgE-induced mast cell activity during cell culture and food allergy. Mast cells were activated via IgE and antigen and the effects of PDI inhibition on mast cell activation were assessed. The effects of PDI blockade in vivo were examined by treating mice with the irreversible PDI inhibitor, PACMA-31, in an ovalbumin-induced model of food allergy. The role of dietary PDI modulators was investigated using various dietary compounds including curcumin and quercetin-3-rutinoside (rutin). PDI expression was observed on resting mast cell surfaces, intracellularly, and in the intestines of allergic mice. Furthermore, enhanced secretion of extracellular PDI was observed on mast cell membranes during IgE and antigen activation. Insulin turbidimetric assays demonstrated that curcumin is a potent PDI inhibitor and pre-treatment of mast cells with curcumin or established PDI inhibitors such as bacitracin, rutin or PACMA-31, resulted in the suppression of IgE-mediated activation and the secretion of various cytokines. This was accompanied by decreased mast cell proliferation, FcεRI expression, and mast cell degranulation. Similarly, treatment of allergic BALB/c mice with PACMA-31 attenuated the development of food allergy resulting in decreased allergic diarrhea, mast cell activation, and fewer intestinal mast cells. The production of TH2-specific cytokines was also suppressed. Our observations suggest that PDI catalytic activity is essential in the regulation of mast cell activation, and that its blockade may benefit patients with allergic inflammation.

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