Extracts of GK-1 Induce Foxp3T Cells in Food-allergic Mice by an IL-4-dependent or IL-4-independent Mechanism

The biological activities of acetic acid bacteria (AAB) as Gram-negative bacteria have attracted our interests, especially in their inhibitory effects on allergic responses. To clarify the underlying mechanism that improves allergic symptoms by ingestion of the AAB , we examined whether different extracts of heat-killed GK-1 could reduce the interleukin (IL)-4 production of immune cells from food-allergic model of OVA23-3, transgenic mice with ovalbumin (OVA)-specific T-cell-receptor genes. A hot-water extract fraction (FII) of GK-1 significantly decreased the IL-4 production of spleen cells of OVA23-3 mice compared with those stimulated with OVA alone. The IL-4 inhibitory effect was also observed for FIV (purified lipopolysaccharide (LPS) fraction), but the activity was lower than for FII or LPS from . Unlike LPS from , FIV significantly inhibited the LPS-induced IL-6 production of the spleen cells. The addition of FII or FIV to a Foxp3T cell-inducing culture showed that FII significantly promoted the rate of Foxp3CD4T cells of OVA-stimulated mesenteric lymph node cells from recombination-activating-gene (RAG)-2-deficient food-allergic inflammatory OVA23-3 (R23-3) mice with suppression of IL-4 production, while FIV induced Foxp3T cells from RAG-2-deficient DO11.10 non-inflammatory mice. Structure analysis showed a lack of O-antigen in FIV, which seemed to lead to the weak biological activities of FIV observed. The present study suggests that extracts of GK-1 to inhibit IL-4 production of immune cells and/or promote regulatory T cell differentiation synergistically play important roles in improving allergic symptoms safely as well as normal condition.