Advances and highlights in mechanisms of allergic disease in 2015

Akdiş, Cezmi A.; Finkelman, Fred D.; Rothenberg, Marc E.

doi:10.1016/j.jaci.2016.02.010

Cited by 35 publications

(20 citation statements)

References 153 publications

(178 reference statements)

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“…This is consistent with the notion that bronchial epithelial hyperplasia, smooth muscle layer thickening, and increased number of mucus-producing cells are key components of airway remodeling occurring in allergic asthma [2, 45]. Interestingly, mice that received c-kit + cells exhibited lowered proliferation index of both bronchial epithelium and airway SMCs together with the decrease in the number of goblet cells.…”

Section: Discussionsupporting

confidence: 88%

New Role of Adult Lung c-kit⁺Cells in a Mouse Model of Airway Hyperresponsiveness

Spaziano

Cappetta

Urbanek

et al. 2016

Mediators of Inflammation

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Structural changes contribute to airway hyperresponsiveness and airflow obstruction in asthma. Emerging evidence points to the involvement of c-kit+ cells in lung homeostasis, although their potential role in asthma is unknown. Our aim was to isolate c-kit+ cells from normal mouse lungs and to test whether these cells can interfere with hallmarks of asthma in an animal model. Adult mouse GFP-tagged c-kit+ cells, intratracheally delivered in the ovalbumin-induced airway hyperresponsiveness, positively affected airway remodeling and improved airway function. In bronchoalveolar lavage fluid of cell-treated animals, a reduction in the number of inflammatory cells and in IL-4, IL-5, and IL-13 release, along with an increase of IL-10, was observed. In MSC-treated mice, the macrophage polarization to M2-like subset may explain, at least in part, the increment in the level of anti-inflammatory cytokine IL-10. After in vitro stimulation of c-kit+ cells with proinflammatory cytokines, the indoleamine 2,3-dioxygenase and TGFβ were upregulated. These data, together with the increased apoptosis of inflammatory cells in vivo, indicate that c-kit+ cells downregulate immune response in asthma by influencing local environment, possibly by cell-to-cell contact combined to paracrine action. In conclusion, intratracheally administered c-kit+ cells reduce inflammation, positively modulate airway remodeling, and improve function. These data document previously unrecognized properties of c-kit+ cells, able to impede pathophysiological features of experimental airway hyperresponsiveness.

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Section: Discussionsupporting

confidence: 88%

New Role of Adult Lung c-kit⁺Cells in a Mouse Model of Airway Hyperresponsiveness

Spaziano

Cappetta

Urbanek

et al. 2016

Mediators of Inflammation

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“…As for humoral mechanisms, generation of allergen-specific IgG4 is especially associated with the development of tolerance to foods in humans. Clinical tolerance induced by immunotherapy is associated with changes in basophils, IgG4, allergen-specific Th2 cells, and allergen-specific cells with regulatory markers 7677. A more complete understanding of mechanisms underlying the induction of oral tolerance with immunotherapy or natural tolerance to food allergens in healthy individuals will help develop better treatment options for patients suffering from food allergies.…”

Section: Resultsmentioning

confidence: 99%

Role of Regulatory Cells in Oral Tolerance

Wawrzyniak

O’Mahony

Akdiş

2017

Allergy Asthma Immunol Res

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The immune system is continuously exposed to great amounts of different antigens from both food and intestinal microbes. Immune tolerance to these antigens is very important for intestinal and systemic immune homeostasis. Oral tolerance is a specific type of peripheral tolerance induced by exposure to antigen via the oral route. Investigations on the role of intestinal immune system in preventing hypersensitivity reactions to innocuous dietary and microbial antigens have been intensively performed during the last 2 decades. In this review article, we discuss how food allergens are recognized by the intestinal immune system and draw attention to the role of regulatory T (Treg) and B (Breg) cells in the establishment of oral tolerance and tolerogenic features of intestinal dendritic cells. We also emphasize the potential role of tonsils in oral tolerance induction because of their anatomical location, cellular composition, and possible usage to develop novel ways of specific immunotherapy for the treatment of allergic diseases.

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“…20 Increased risk of eczema and FA is associated with filaggrin mutation, which is a loss-of-function mutation that leads to dysfunctions in the skin barrier. 21 Sensitization through the skin is thought to increase likelihood of peanut allergy in individuals with filaggrin loss-of-function mutation exposed to environmental dust containing peanuts. It has also been hypothesized that the introduction of fruits and vegetables containing fermentable fiber in early infancy could increase microbial diversity and short-chain fatty acids, which are known to promote epithelial integrity and reduce penetration of intact food allergens.…”

Section: Overview Of Mechanism Of Allergic Response In the Gastrointementioning

confidence: 99%

Deciphering the black box of food allergy mechanisms

Sampath

Tupa

Graham

et al. 2017

Annals of Allergy, Asthma & Immunology

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Objective To review our current understanding of immunotherapy, the immune mechanisms underlying food allergy, and the methodological advances that are furthering our understanding of the role of immune cells and other molecules in mediating food allergies. Data Sources Literature searches were performed using the following combination of terms: allergy, immunotherapy, food, and mechanisms. Data from randomized clinical studies using state-of-the-art mechanistic tools were prioritized. Study Selections Articles were selected based on their relevance to food allergy. Results Current standard of care for food allergies is avoidance of allergenic foods and the use of epinephrine in case of severe reaction during unintentional ingestion. During the last few decades, great strides have been made in understanding the cellular and molecular mechanisms underlying food allergy, and this information is spearheading the development of exciting new treatments. Conclusion Immunotherapy protocols are effective in desensitizing individuals to specific allergens; however, recurrence of allergic sensitization is common after discontinuation of therapy. Interestingly, in a subset of individuals, immunotherapy is protective against allergens even after discontinuation of immunotherapy. Whether this protection is permanent is currently unknown because of inadequate long-term follow-up data. Research on understanding the underlying mechanisms may assist in modifying protocols to improve outcome and enable sustained unresponsiveness, rather than a temporary relief against food allergies. The cellular changes brought about by immunotherapy are still a black box, but major strides in our understanding are being made at an exciting pace.

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Advances and highlights in mechanisms of allergic disease in 2015

Cited by 35 publications

References 153 publications

New Role of Adult Lung c-kit⁺Cells in a Mouse Model of Airway Hyperresponsiveness

New Role of Adult Lung c-kit⁺Cells in a Mouse Model of Airway Hyperresponsiveness

Role of Regulatory Cells in Oral Tolerance

Deciphering the black box of food allergy mechanisms

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Advances and highlights in mechanisms of allergic disease in 2015

Cited by 35 publications

References 153 publications

New Role of Adult Lung c-kit+Cells in a Mouse Model of Airway Hyperresponsiveness

New Role of Adult Lung c-kit+Cells in a Mouse Model of Airway Hyperresponsiveness

Role of Regulatory Cells in Oral Tolerance

Deciphering the black box of food allergy mechanisms

Contact Info

Product

Resources

About

New Role of Adult Lung c-kit⁺Cells in a Mouse Model of Airway Hyperresponsiveness

New Role of Adult Lung c-kit⁺Cells in a Mouse Model of Airway Hyperresponsiveness