PurposeProbiotic bacteria can induce immune regulation or immune tolerance in allergic diseases. The underlying mechanisms have been recently investigated, but are still unclear. The aim of this study was to evaluate the protective effects of the probiotic Lactobacillus rhamnosus (Lcr35) in a mouse model of asthma and to identify its mechanism of action.MethodsLcr35 was administered daily by the oral route at a dosage of 1×109 CFU/mouse in BALB/c mice for 7 days before the first sensitization. Clinical parameters and regulatory T (Treg) cells were examined. The role of CD4+CD25+Foxp3+ Treg cells was analyzed using a Treg cell-depleting anti-CD25 monoclonal antibody (mAb).ResultsAirway hyperresponsiveness, total IgE production, pulmonary eosinophilic inflammation, and splenic lymphocyte proliferation were suppressed after Lcr35 treatment. Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines in the serum were suppressed, and the percentage of CD4+CD25+Foxp3+ Treg cells in the spleen was significantly increased in the Lcr35 treatment group. Anti-CD25 mAb administration abolished the protective effects of Lcr35, indicating that CD4+ CD25+Foxp3+ Treg cells are essential in mediating the activity of Lcr35.ConclusionsOral administration of Lcr35 attenuated the features of allergic asthma in a mouse model and induced immune regulation by a CD4+CD25+Foxp3+ Treg cell-mediated mechanism.

The gasdermin A (GSDMA) and gasdermin B (GSDMB) genes are located at 17q21.2. The GSDM family genes have been studied in the gastrointestinal tract but recent reports suggest that GSDMB is associated with childhood asthma in several populations. We investigated the association of the GSDMA and GSDMB variants with asthma in Korean children, and to assess the effect of these variants on intermediate phenotypes of asthma. Asthmatic (n = 778) and normal (n = 522) children were enrolled and genotypes were determined using PCR-RFLP. Asthma susceptibility was associated with GG of the GSDMA (rs7212938) and TT of GSDMB (rs7216389). And a combination of risk alleles of two polymorphisms was associated with asthma susceptibility and a frequency of those was higher in asthmatic children with increased levels of total IgE (aOR 1.77, 95% CI 1.15-2.72) and BHR (aOR 1.54, 95% CI 0.99-2.40) compared to normal. Also, we observed a significant association between haplotype of two polymorphisms and asthma susceptibility. The region including the GSDMA and GSDMB polymorphisms may be associated with asthma susceptibility and intermediate phenotypes of asthma, such as elevated IgE and BHR, in Korean children with asthma. These results strongly support an important role for the GSDMA and GSDMB in the development of childhood asthma.