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 ◽  
...  

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.

Immunity ◽  
2015 ◽  
Vol 43 (4) ◽  
pp. 788-802 ◽  
Author(s):  
Chun-Yu Chen ◽  
Jee-Boong Lee ◽  
Bo Liu ◽  
Shoichiro Ohta ◽  
Pin-Yi Wang ◽  
...  

2014 ◽  
Vol 35 (4) ◽  
pp. 285-293 ◽  
Author(s):  
Ji-Hyun KIM ◽  
Takeshi YAMAMOTO ◽  
Jaemin LEE ◽  
Tomoe YASHIRO ◽  
Takayuki HAMADA ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2660 ◽  
Author(s):  
Yui-Hsi Wang

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.


2015 ◽  
Vol 192 ◽  
pp. 59
Author(s):  
T. Yashiro ◽  
H. Ogata ◽  
T. Yamamoto ◽  
M. Kadowaki

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e85888 ◽  
Author(s):  
Takeshi Yamamoto ◽  
Toshihisa Kodama ◽  
Jaemin Lee ◽  
Naho Utsunomiya ◽  
Shusaku Hayashi ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Anuya Paranjape ◽  
Mindy Tsai ◽  
Kaori Mukai ◽  
Ramona A. Hoh ◽  
Shilpa A. Joshi ◽  
...  

Basophil activation tests (BATs) can closely monitor, in vitro, a patient’s propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients’ basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE+ plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies.


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