Latilactobacillus sakei Wikim0185 alleviates allergic asthma by inducing tolerogenic dendritic cells through epigenetic rewriting

Kimchi is a traditional Korean food widely recognized for its probiotic properties and potential health benefits. Several lactic acid bacteria (LAB) from Kimchi exhibit immunomodulatory properties, and their efficacy has been evaluated for various immune-related diseases. However, the mechanisms underlying the immunomodulatory effects of LAB are not yet fully understood. In this study, we demonstrated the immunomodulatory effects of Latilactobacillus sakei Wikim0185, isolated from sweet potato Kimchi, in an ovalbumin (OVA)-induced allergic asthma mouse model by inducing tolerogenic dendritic cells (DCs) and regulatory T cells (Tregs). Bone marrow-derived dendritic cells (BMDCs) and OVA-peptide-stimulated splenocytes isolated from OT-II mice co-cultured with Wikim0185 exhibited increased secretion of the anti-inflammatory cytokine IL-10. Oral administration of Wikim0185 in allergic asthma experimental mice alleviated symptoms, including airway hyperresponsiveness (AHR), leukocyte infiltration, and reduced Th2-type cytokine levels in bronchoalveolar lavage (BAL) fluid. Notably, Wikim0185-treated mice displayed an increased proportion of Foxp3+ Tregs in mediastinal lymph nodes. Additionally, mediastinal lymph node cells restimulated with OVA exhibited decreased secretion of Th2-type cytokines while showing increased IL-10 production. Interestingly, RNA sequencing and chromatin immunoprecipitation (ChIP)-qPCR analysis revealed that Wikim0185 induced tolerogenic DCs through epigenetic histone modifications, increasing active chromatin marks (H3K4me3, H3K9ac, and H3K27ac) on the promoter regions of tolerogenic marker genes (Pdl1, Il10, Socs1, and Socs3). These findings suggest that Wikim0185 modulates immune responses by epigenetically reprogramming DCs, thereby promoting Treg differentiation and suppressing excessive Th2 immune responses in an allergic asthma mouse model. RNA-seq profiling of bone marrow derived dendritic cells and co-cultured with PBS or Latilactobacillus sakei Wikim0185 for 6 hours.