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Abstract: Background: The mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors. Objectives: We hypothesized that the T‐cell gut‐homing receptor CCR9 could be implicated in the evolution of allergic diseases. Methods: We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite. Results: Compared with solely asthmatic‐like mice, we demonstrated that the aggravation of pulmonary symptoms in consecutive food and respiratory allergies, characterized by an increase in pulmonary resistance and a higher Th17/Treg ratio, was abrogated in CCR9 knockout mice. Moreover, transfer of food‐allergic CD4+ T cells from wild‐type but not from CCR9−/− aggravated airways inflammation demonstrating that CCR9 is involved in food allergy‐enhanced allergic airway inflammation to unrelated allergens. Conclusion: Taken together, our results demonstrated a crucial role of the T‐cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases. [ABSTRACT FROM AUTHOR]

Background Exposure to respiratory allergens triggers airway hyperresponsiveness and inflammation characterized by the expansion of TH2 cells and the production of allergen specific IgE. Allergic asthma is characterized by an alteration in immune regulatory mechanisms leading to an imbalance between pro- and anti-inflammatory components of the immune system. Aims Recently B cells have been described as central regulators of exacerbated inflammation, notably in the case of autoimmunity. However, to what extent these cells can regulate airway inflammation and asthma remains to be elucidated. Materials & Methods We took advantage of a allergic asthma model in mice induced by percutaneous sensitization and respiratory challenge with an extract of house dust mite. Results In this study, we showed that the induction of allergic asthma alters the homeostasis of IL-10+ Bregs and favors the production of inflammatory cytokines by B cells. Deeper transcriptomic and phenotypic analysis of Bregs revealed that they were enriched in a CD9+ B cell subset. In asthmatic mice the adoptive transfer of CD9+ B cells normalized airway inflammation and lung function by inhibiting TH2- and TH17-driven inflammation in an IL-10-dependent manner, restoring a favorable immunological balance in lung tissues. Indeed we further showed that injection of CD9+ Bregs controls the expansion of lung effector T cells allowing the establishment of a favorable regulatory T cells/effector T cells ratio in lungs. Conclusion This finding strengthens the potential for Breg-targeted therapies in allergic asthma. [ABSTRACT FROM AUTHOR]

Background: The mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors., Objectives: We hypothesized that the T-cell gut-homing receptor CCR9 could be implicated in the evolution of allergic diseases., Methods: We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite., Results: Compared with solely asthmatic-like mice, we demonstrated that the aggravation of pulmonary symptoms in consecutive food and respiratory allergies, characterized by an increase in pulmonary resistance and a higher Th17/Treg ratio, was abrogated in CCR9 knockout mice. Moreover, transfer of food-allergic CD4 + T cells from wild-type but not from CCR9 -/- aggravated airways inflammation demonstrating that CCR9 is involved in food allergy-enhanced allergic airway inflammation to unrelated allergens., Conclusion: Taken together, our results demonstrated a crucial role of the T-cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Exposure to respiratory allergens triggers airway hyperresponsiveness and inflammation characterized by the expansion of TH 2 cells and the production of allergen specific IgE. Allergic asthma is characterized by an alteration in immune regulatory mechanisms leading to an imbalance between pro- and anti-inflammatory components of the immune system., Aims: Recently B cells have been described as central regulators of exacerbated inflammation, notably in the case of autoimmunity. However, to what extent these cells can regulate airway inflammation and asthma remains to be elucidated., Materials & Methods: We took advantage of a allergic asthma model in mice induced by percutaneous sensitization and respiratory challenge with an extract of house dust mite., Results: In this study, we showed that the induction of allergic asthma alters the homeostasis of IL-10(+) Bregs and favors the production of inflammatory cytokines by B cells. Deeper transcriptomic and phenotypic analysis of Bregs revealed that they were enriched in a CD9(+) B cell subset. In asthmatic mice the adoptive transfer of CD9(+) B cells normalized airway inflammation and lung function by inhibiting TH 2- and TH 17-driven inflammation in an IL-10-dependent manner, restoring a favorable immunological balance in lung tissues. Indeed we further showed that injection of CD9(+) Bregs controls the expansion of lung effector T cells allowing the establishment of a favorable regulatory T cells/effector T cells ratio in lungs., Conclusion: This finding strengthens the potential for Breg-targeted therapies in allergic asthma., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)