B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3

Aeroallergen sensitization,mainly mediated by lung epithelium and dendritic cells(DCs),is integral to allergic asthma pathogenesis and progression.IL-10 has a dual role in immune responses,as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation.Here,we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma.Specifically,Bcl-3^(−/−)mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites(HDMs).IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial cells.Blockade of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma development.IL-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3–Blimp-1–Bcl-6 regulation.Mice lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization,thereby demonstrating resistance to HDM-induced asthma.Moreover,responses to HDM stimulation in Bcl-3^(−/−)mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3^(+/+)mice.The results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 production.Thus,targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma.

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v I using a gnotobiotic mouse model. We showed that Lactobacillus （L.） rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 （TLR2） and nucleotide-binding oligomerization domain-containing protein 2 （NOD2） receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free （GF） mice with a mixture of all three strains （Lmix） improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v I allergen showed significantly lower levels of allergen-specific IgE, IgG 1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor （TGF）-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans,

Allergen specifi c sublingual immunotherapy in children with asthma and allergic rhinitis

Background:The incidence of asthma and allergic rhinitis(AR)is significantly increased,especially in younger children.Current treatment for children with asthma and allergic rhinitis include allergen avoidance,standard pharmacotherapy,and immunotherapy.Since standard pharmacotherapy is prescribed for symptoms,immunotherapy at present plays an important role in the treatment of allergic diseases.This article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and asthma.Data sources:PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms"asthma","allergic rhinitis","children",and"immune therapy".Additional articles were identified by hand searching of the references in the initial search.Results:Numerous studies have shown that sublingual application of allergen specifi c immunotherapy(SLIT)is an adequate,safe and effi cient substitution to subcutaneous route of allergens administration(SCIT)in the treatment of IgE-mediated respiratory tract allergies in children.According to the literature,better clinical efficacy is connected with the duration of treatment and mono sensitized patients.Conclusions:At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT.SLIT reduces the symptoms of allergic diseases and the use of medicaments,and improves the quality of life of children with the diseases.