Phagocytes such as dendritic cells and macrophages, which are distributed in the small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis by sampling the luminal gut microbiota. However, there is limited information regarding microbial uptake in a steady state. We investigated the composition of murine gut microbiota that is engulfed by phagocytes of specific subsets in the small intestinal lamina propria (SILP) and Peyer’s patches (PP). Analysis of bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte subsets in the SILP primarily engulfed Lactobacillus (the most abundant microbe in the small intestine), whereas CD11bhi and CD11bhiCD11chi cell subsets in PP mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents that are reported to adhere to intestinal epithelial cells); and 2) among the Lactobacillus species engulfed by the SILP cell subsets, L. murinus was engulfed more frequently than L. taiwanensis, although both these Lactobacillus species were abundant in the small intestine under physiological conditions. These results suggest that small intestinal microbiota is selectively engulfed by phagocytes that localize in the adjacent intestinal mucosa in a steady state. These observations may provide insight into the crucial role of phagocytes in immune surveillance of the small intestinal mucosa.

T cell receptor α  mutant (TCRα –/–) mice, which spontaneously develop colitis under conventional conditions, did not show any signs of colitis under germ‐free conditions, leaving TCRα –β + cells (β dim cells) and TCRγ δ + cells much reduced. Moreover, TCRα –/– mice with alymphoplastic mutation (aly/aly TCRα –/– mice), which lack Peyer's patches and peripheral lymph nodes, did not suffer from colitis. While both β dim cells and TCRγ δ + cells were present in the colons of aly/aly TCRα –/– mice and aly/+ TCRα –/– mice, cytotoxicity of colonic TCRγ δ + cells in aly/aly TCRα –/– mice was almost abolished. Transfer of TCRγ δ + cells from TCRα –/– mice into scid/scid mice or aly/aly TCRα –/– mice could not induce colitis, but injection of anti‐TCRδ  mAb into TCRα –/– mice prevented colitis from developing. Finally, TCRα –/– mice expressing transgenic (Tg) KN6‐TCRγ δ  hardly developed colitis, accompanied by colonization of non‐cytotoxic Tg TCRγ δ + cells in their colonic mucosa. These results demonstrate that intestinal resident TCRγ δ + cells may be involved in the exacerbation of inflammatory bowel disease in TCRα –/– mice.

Recently, the prevalence of allergies in Japan has been increasing. Certain types of fruit juice and lactic acid bacteria are known to alleviate allergic symptoms. Therefore, we examined whether citrus juice fermented by a specific lactic acid bacteria can improve the symptoms of Japanese cedar pollinosis (JCPsis). Lactobacillus plantarum YIT 0132 (LP0132) was selected based on its high proliferative activity in citrus juice and anti-inflammatory interleukin-10-inducing activity. Dietary administration of heat-killed LP0132 cells or citrus juice fermented with LP0132 was found to significantly suppress nasal rubbing in a JCPsis mouse model, indicating relief of allergy symptoms. To evaluate the effects of LP0132-fermented citrus juice on pollinosis symptoms and quality of life (QOL) in humans with JCPsis, a single-blind, placebo-controlled, parallel-group clinical trial was conducted. The participants were 42 adults with JCPsis. They ingested 100 mL of sterilized LP0132-fermented citrus juice (active group) or unfermented citrus juice (placebo group) once daily for 8 weeks. Immediately after the pollen peak when allergy symptoms and QOL loss were most severe, itchy eyes, itchy skin, and QOL loss by JCPsis were alleviated in the active group compared with the placebo group. At 10 weeks after starting the intervention, increased the levels of blood eosinophils were significantly suppressed in the active group compared with the placebo group. We conclude that continuous ingestion of citrus juice fermented with LP0132 may help alleviate the allergy symptoms and impaired QOL caused by JCPsis.

Immunoglobulin A (IgA) is transported by the polymeric immunoglobulin receptor (pIgR) through epithelial cells of the gut, the airways, the tear and salivary glands, and the lactating mammary gland, and IgA accumulates in serum and the intestinal lamina propria of pIgR‐deficient (pIgR–/–) mice. Intraepithelial lymphocytes (IEL) increased in number and Thy‐1+CD8αβ+TCRαβ+ IEL preferentially expanded in the small intestine (SI) of pIgR–/– mice. Cytotoxic activity of SI‐IEL was comparable in pIgR+/+ and pIgR–/– mice. Accumulation and cytotoxic activity of SI‐IEL was attenuated in germ‐free pIgR–/– mice. Furthermore, Thy‐1+CD8αβ+ IEL did not expand in pIgR–/–TCRβδ–/– mice compared with TCRβδ–/– mice, and SI‐IEL from pIgR–/–TCRβδ–/– mice as well as TCRβδ–/– mice expressed perforin and granzyme B mRNA and serine esterase. The proliferative status of SI‐IEL from pIgR+/+ and pIgR–/– mice was similar, but adoptive transfer experiment showed that SI‐IEL from pIgR–/– mice might have a stronger tendency to migrate into the intestinal epithelia than those from pIgR+/+ mice. These results demonstrate that the accumulation of Thy‐1+CD8αβ+TCRαβ+ IEL in pIgR–/– mice triggered by intestinal microorganisms needed the expression of functional TCR and might be caused by lymphocyte migration into the intestinal epithelia.

Summary To clarify the effect of secretory IgA (sIgA) deficiency on gut homeostasis, we examined intraepithelial lymphocytes (IELs) in the small intestine (SI) of polymeric immunoglobulin receptor‐deficient (pIgR−/−) mice. The pIgR−/− mice exhibited the accumulation of CD8αβ+ T‐cell receptor (TCR)‐αβ+ IELs (CD8αβ+αβ‐IELs) after weaning, but no increase of CD8αβ+γδ‐IELs was detected in pIgR−/− TCR‐β−/− mice compared with pIgR+/+ TCR‐β−/− mice. When 5‐bromo‐2′‐deoxyuridine (BrdU) was given for 14 days, the proportion of BrdU‐labelled cells in SI‐IELs was not different between pIgR+/+ mice and pIgR−/− mice. However, the proportion of BrdU‐labelled CD8αβ+‐IELs became higher in pIgR−/− mice than pIgR+/+ mice 10 days after discontinuing BrdU‐labelling. Intravenously transferred splenic T cells migrated into the intraepithelial compartments of pIgR+/+ TCR‐β−/− mice and pIgR−/− TCR‐β−/− mice to a similar extent. In contrast, in the case of injection of immature bone marrow cells, CD8αβ+αβ‐IELs increased much more in the SI of pIgR−/− TCR‐β−/− mice than pIgR+/+ TCR‐β−/− mice 8 weeks after the transfer. αβ‐IELs from pIgR−/− mice could produce more interferon‐γ and interleukin‐17 than those of pIgR+/+ mice, and intestinal permeability tended to increase in the SI of pIgR−/− mice with aging. Taken together, these results indicate that activated CD8αβ+αβ‐IELs preferentially accumulate in pIgR−/− mice through the enhanced differentiation of immature haematopoietic precursor cells, which may subsequently result in the disruption of epithelial integrity.

No abstract

Recently, the prevalence of allergies in Japan has been increasing. Certain types of fruit juice and lactic acid bacteria are known to alleviate allergic symptoms. Therefore, we examined whether citrus juice fermented by a specific lactic acid bacteria can improve the symptoms of Japanese cedar pollinosis (JCPsis). Lactobacillus plantarum YIT 0132 (LP0132) was selected based on its high proliferative activity in citrus juice and anti-inflammatory interleukin-10-inducing activity. Dietary administration of heat-killed LP0132 cells or citrus juice fermented with LP0132 was found to significantly suppress nasal rubbing in a JCPsis mouse model, indicating relief of allergy symptoms. To evaluate the effects of LP0132-fermented citrus juice on pollinosis symptoms and quality of life (QOL) in humans with JCPsis, a single-blind, placebo-controlled, parallel-group clinical trial was conducted. The participants were 42 adults with JCPsis. They ingested 100 mL of sterilized LP0132-fermented citrus juice (active group) or unfermented citrus juice (placebo group) once daily for 8 weeks. Immediately after the pollen peak when allergy symptoms and QOL loss were most severe, itchy eyes, itchy skin, and QOL loss by JCPsis were alleviated in the active group compared with the placebo group. At 10 weeks after starting the intervention, increased the levels of blood eosinophils were significantly suppressed in the active group compared with the placebo group. We conclude that continuous ingestion of citrus juice fermented with LP0132 may help alleviate the allergy symptoms and impaired QOL caused by JCPsis.

Mononuclear phagocytic cells (MPCs) are classified into monocytes/macrophages and dendritic cells (DCs) based on their functions. Cells of MPCs lineage act as immune modulators by affecting effector cells, such as NK cells, T cells, and B cells. This study aimed to investigate the effects of Lacticaseibacillus paracasei strain Shirota (LcS) ingestion on peripheral MPCs, particularly on their expression of functional cell-surface molecules enhanced in healthy adults. Thus, twelve healthy office workers consumed a fermented milk drink containing 1.0 × 10 11 cfu of LcS (LcS-FM) or a control unfermented milk drink (CM) once a day for 6 weeks. Peripheral blood mononuclear cells (PBMCs) were prepared from blood samples, and immune cells and functional cell-surface molecules were analyzed. We observed remarkable differences in the expression of HLAABC, MICA, CD40, and GPR43 in plasmacytoid DCs (pDCs) between the LcS-FM and CM groups, whereas no difference was found in CD86 or HLA-DR expression. The LcS-FM group exhibited higher CD40 expression in both conventional DCs (cDCs) and monocytes, especially in type 2 conventional DCs (cDC2s) and classical monocytes (cMos); higher percentages of cMos, intermediate monocytes (iMos), and nonclassical monocytes; and higher numbers of cMos and iMos in PBMCs than the CM group. LcS ingestion increased the expression of HLAABC, MICA, CD40, and GPR43 in pDCs and CD40 in cDCs and Mos, particularly cDC2s and cMos. These results suggest that LcS modulates the function of MPCs that may lead to the regulation of immune effector