Biology subjects

Okuno, A.

Publications and source records attributed to Okuno, A..

4 recordsLinked to original sources

bioRxiv2025

Probiotic lactic acid bacteria induce regulatory functions in γδ T cells

While the modulatory effects of probiotic LAB on conventional T cells are well documented, its effects on unconventional T cells, including gamma-delta ({gamma}{delta}) T cells, have not yet been fully characterized. In this study, we show that probiotic LAB has the capacity to generate regulatory {gamma}{delta} T cells. Probiotic LAB stimulation significantly increased interleukin (IL)-10, but not IFN-{gamma} or IL-17A, in {gamma}{delta} T cells compared to stimulation with methicillin-resistant Staphylococcus aureus (MRSA). This regulatory function subsequently attenuated IL-8 production in intestinal epithelial cells. Thus, probiotic LAB can induce regulatory functions in {gamma}{delta} T cells, which may contribute to the maintenance of intestinal health.

immunology↗

bioRxiv2025

Modulation of decodable semantic features of brain activity via selection attention

We frequently encounter linguistic information in multiple modalities, such as text and speech, simultaneously. In such cases, we understand the information by selectively attending to one of the modalities. Previous research has shown that selective attention to a specific stimulus modality modulates cortical activity patterns. However, it remains unclear which aspects of linguistic information are selectively modulated by attention and how such modulation influences the decodability of semantic content. To address this question, we constructed decoding models of latent semantic features from the functional magnetic resonance imaging data of six participants in both unimodal (either visual or auditory) and bimodal conditions (simultaneously visual and auditory, with participants attending to a single modality at a time). In unimodal conditions, we successfully decoded the semantic contents from the brain activity. Decodable features were consistent across modalities in both intra-modal and cross-modal decoding. For bimodal conditions, decoding accuracies for the attended stimuli were higher than for the ignored when training and test stimuli belonged to the same modality. Furthermore, decodable features were more consistent across modalities with attended than ignored stimuli in both intra-modal and cross-modal decoding. These results indicate common decodable semantic features regardless of the presentation modality and that selective attention enhances the semantic representations contributing to such decodability.

neuroscience↗

bioRxiv2024

Lactococcus lactis subsp. cremoris C60 creates a type I regulatory T cell-dominant anti-inflammatory intestinal environment through functional modification of dendritic cells

Lactic acid bacteria (LAB)-mediated probiotics have the capability to modulate intestinal immunity, creating an anti-inflammatory environment. Among the immune-modulatory effects, interleukin (IL)-10-producing CD4+ T cells are often discussed for their anti-inflammatory roles. While regulatory T cells (Tregs) are a well-known subset, type I regulatory T (Tr1) cells, which also produce abundant IL-10, receive less attention in LAB-induced anti-inflammatory effects. Here, we report that Lactococcus lactis subsp. cremoris C60, a probiotic LAB strain, increases IL-10-producing Tr1 cells in the intestinal environment, contributing to resistance against inflammatory conditions such as dextran sodium sulfate (DSS)-induced colitis. Intragastric administration of heat-killed (HK)-C60 significantly increased IL-10+CD4+ T cells in intestinal tissues compared to control treatment. These populations predominantly consisted of Forkhead box protein P3 (Foxp3)-negative cells, indicating that Tr1 cells were primarily expanded by HK-C60 stimulation. Further analysis revealed that IL-10+ Tr1 cells could be classified into two major subpopulations: IL-10 single-positive (SP) and IFN-{gamma}/IL-10 double-positive (DP) cells. An in vitro co-culture system using CD4+ T cells and bone marrow-derived dendritic cells (BMDCs) demonstrated that HK-C60 stimulation modified dendritic cell function, promoting Tr1 cell differentiation. Moreover, pro-inflammatory IFN-{gamma}+CD4+ T (Th1) cells differentiated into IL-10+ Tr1 cells in the presence of HK-C60-stimulated BMDCs, with the effect being particularly pronounced in DP Tr1 cells. HK-C60-administration attenuated inflammation and reduced pro-inflammatory leukocyte infiltration in the colon of DSS-induced colitis mice, accompanied by the expansion of DP Tr1 cells. The suppressive effect of intestinal CD4+ T cells in HK-C60-treated mice was IL-10-dependent, as demonstrated by an in vitro IL-10 neutralizing assay. Thus, C60-based probiotics promote the creation of an anti-inflammatory intestinal environment by increasing IL-10+ Tr1 cells rather than Tregs.

immunology↗

bioRxiv2024

Lactococcus lactis subsp. cremoris C60 promotes immunoglobulin A production from B cells through functional modification of dendritic cells in intestinal environment

Probiotics utilizing lactic acid bacteria (LAB) have gained considerable attention in recent trends promoting self-managed health. Specifically, LAB-mediated immune modulation has been a key focus due to its potential to reduce the risk of pathogenic invasion and enhance host immunity. Immunoglobulin A (IgA) plays a crucial role in innate defense against various pathogens. Although only a limited number of probiotic LAB strains have been shown to increase IgA production, this capability remains of great interest. Here, we report a new strain, Lactococcus lactis subsp. cremoris C60 (C60), which promotes IgA production through functional modulation of intestinal B cells and dendritic cells (DCs). Heat-killed (HK)-C60 increased both pro-inflammatory and anti-inflammatory cytokine productions in DCs via the Toll-like receptor (TLR)-Myeloid differentiation primary response 88 (MyD88) signaling pathway, as demonstrated in both a physiological mouse model and in vitro cultures using bone marrow-derived dendritic cells (BMDCs). Notably, intragastric administration of HK-C60 significantly increased systemic IgA production, which was associated with the functional modification of B cells in the Peyers patches (PPs) of the small intestine. Immunophenotyping of PP cells from HK-C60-administered mice revealed both an expansion and functional upregulation of B cells. Mechanistically, we identified that DC-derived interleukin-6 (IL-6) and IL-10 play essential roles in the C60-mediated increase in IgA production by B cells. Finally, we evaluated the effect of C60 on IgA production using human peripheral blood mononuclear cells (PBMCs). Consistent with our findings in the mouse model, PBMCs produced IgA upon HK-C60 stimulation in an IL-6- and IL-10-dependent manner. Our results suggest that C60 is a novel probiotic strain capable of promoting intestinal immune homeostasis by upregulating IgA production, underscoring its potential for probiotic applications focused on immune conditioning.

immunology↗