Oral tolerance inhibits atopic dermatitis-like type 2 inflammation in mice by modulating immune microenvironments

Baek, Jeong‐Heum; Roh, Joo‐Young; Jung, YunJae

doi:10.1111/all.12960

Cited by 19 publications

(30 citation statements)

References 47 publications

(59 reference statements)

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“…However, the production of both Th1 and Th2 type cytokines, and IL-10 from tolerized murine lymphoid cells was suppressed, suggesting the induction of T cell anergy. The dosage of the ingested antigen for inducing oral tolerance in this study was comparatively higher to that used in the previous studies mentioned above [31, 32]. Low doses of antigen ingestion are known to favor the induction of active suppression, whereas high doses favor the induction of anergy [33].…”

Section: Discussion/conclusionmentioning

confidence: 94%

“…Baek et al [31] reported that the prior ingestion of ovalbumin (OVA) induced Foxp3 + Treg cells in an OVA-epicutaneously sensitized mouse model. Likewise, van Esch et al [32] reported that the numbers of Foxp3 + Treg cells in the MLN were increased in whey protein hydrolysate-induced tolerized mice, and transfer of MLN cells from these tolerized mice protected the recipient mice from developing an allergic response.…”

Section: Discussion/conclusionmentioning

confidence: 99%

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Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice

Iwamoto

Matsubara

Okamoto

et al. 2019

Int Arch Allergy Immunol

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Background: Casein is the most dominant causal allergen in cow’s milk allergy (CMA). Casein hydrolysates are frequently applied in infant formulas for children with a risk or history of CMA. However, there is limited information on the oral tolerance-inducing ability of casein hydrolysates. Objectives: The aim of this study was to investigate whether the ingestion of casein hydrolysate induces tolerance to casein, ultimately preventing subsequent epicutaneous sensitization and development of an anaphylaxis reaction. Methods: BALB/c mice were orally administered casein or a casein hydrolysate (CNH) via the drinking water and were then epicutaneously sensitized by repeated exposure of casein on tape-stripped skin. Sensitization was assessed by basophil activation tests, the serum levels of casein-specific antibodies, and cytokine production from casein-stimulated spleen and mesenteric lymph node (MLN) cells. Occurrence of an anaphylaxis reaction was evaluated by measuring rectal temperature and the plasma level of mouse mast cell protease-1 (mMCP-1) after oral casein challenges. The T cell population in the spleen and MLN was assessed by flow cytometry. Intestinal mast cells and basophils were analyzed histologically. Results: Sensitization and anaphylaxis reaction to casein were significantly suppressed in casein- or CNH-fed mice compared to controls. Prior ingestion of casein or CNH had no effect on the population of regulatory T cells and activated T cells in lymphoid tissues. Intestinal basophils increased by the epicutaneous sensitization of casein, which was suppressed in casein- or CNH-fed mice. Although the increase in the plasma level of mMCP-1 after oral challenge was suppressed in casein- or CNH-fed mice, there was no change in the number of intestinal mast cells. Conclusion: Prior ingestion of casein or CNH induced oral tolerance and suppressed subsequent epicutaneous sensitization and development of systemic anaphylaxis to casein.

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Section: Discussion/conclusionmentioning

confidence: 94%

Section: Discussion/conclusionmentioning

confidence: 99%

Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice

Iwamoto

Matsubara

Okamoto

et al. 2019

Int Arch Allergy Immunol

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“…Interestingly, it has been shown that filaggrin mutant mice spontaneously develop AD which was mediated by IL‐5 producing ILC2s in the skin and independent of adaptive immunity . The effects of tolerance on ILC2s are mainly unknown; however, a recent study showed that oral tolerance inhibited the type‐2 inflammation including ILC2s in an ovalbumin‐driven‐AD model in mice …”

Section: Role Of Ilc2s In Disease Pathogenesismentioning

confidence: 99%

Type two innate lymphoid cells: the Janus cells in health and disease

Maazi

Akbari

2017

Immunological Reviews

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Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease.

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“…Allergen-specific oral tolerance could be achieved in an atopic dermatitis mouse model epicutaneously sensitized to ovalbumin, with practical implications in human atopic dermatitis patients suffering from exacerbations due to the intake of dietary allergens [25]. A study in atopic dogs, which represent a relevant model for human atopic dermatitis [3], demonstrated that a chemokine receptor-4 antagonist prevented homing of lymphocytes into the lesional skin [26].…”

Section: Atopic Dermatitis Modelsmentioning

confidence: 99%

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

Jensen‐Jarolim

Pali‐Schöll

Roth‐Walter

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewAnimal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases.Recent findingsAllergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment.SummaryIn atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.

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Oral tolerance inhibits atopic dermatitis-like type 2 inflammation in mice by modulating immune microenvironments

Abstract: Oral tolerance plays a protective role in the development of AD in a murine model by modulating immune microenvironments to be more favorable for immune regulation. This modulation involves inhibition of ILC2 infiltration in skin lesions.

Cited by 19 publications

References 47 publications

Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice

Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice

Type two innate lymphoid cells: the Janus cells in health and disease

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

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