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Biomedical subjects

Masanobu Nanno

Publications and source records attributed to Masanobu Nanno.

11 recordsLinked to original sources
PubMed2005

Prenatal blockage of lymphotoxin beta receptor and TNF receptor p55 signaling cascade resulted in the acceleration of tissue genesis for isolated lymphoid follicles in the large intestine.

Signaling by lymphotoxin (LT) and TNF is essential for the organogenesis of secondary lymphoid tissues in systemic and mucosal compartments. In this study, we demonstrated that the progeny of mice treated with fusion protein of LTbetaR and IgGFc (LTbetaR-Ig) or LTbetaR-Ig plus TNFR55-Ig (double Ig) showed significantly increased numbers of isolated lymphoid follicles (ILF) in the large intestine. Interestingly, double Ig treatment accelerated the maturation of large intestinal ILF. Three-week-old progeny of double Ig-treated mice showed increased numbers of ILF in the large intestine, but not in the small intestine. Furthermore, alteration of intestinal microflora by feeding of antibiotic water did not affect the increased numbers of ILF in the large intestine of double Ig-treated mice. Most interestingly, mice that developed numerous ILF also had increased levels of activation-induced cytidine deaminase expression and numbers of IgA-expressing cells in the lamina propria of the large intestine. Taken together, these results suggest that ILF formation in the large intestine is accelerated by blockage of LTbetaR and TNFR55 signals in utero, and ILF, like colonic patches, might play a role in the induction of IgA response in the large intestine.

Animals↗
PubMed2005

Accumulation of intestinal intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptor.

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(+)CD8alphabeta(+)TCRalphabeta(+) 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(+)CD8alphabeta(+) IEL did not expand in pIgR(-/-)TCRbetadelta(-/-) mice compared with TCRbetadelta(-/-) mice, and SI-IEL from pIgR(-/-)TCRbetadelta(-/-) mice as well as TCRbetadelta(-/-) 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(+)CD8alphabeta(+)TCRalphabeta(+) 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.

Animals↗
PubMed2005

Modulation of natural killer cell activity by supplementation of fermented milk containing Lactobacillus casei in habitual smokers.

BACKGROUND: Habitual smoking significantly reduces natural killer (NK) cell activity. To clarify whether the intake of fermented milk containing lactic acid bacteria restores NK cell activity in habitual smokers, we conducted a placebo-controlled double-blind test. METHODS: Ninety-nine subjects with smoking habits were randomly divided into two groups and daily for 3 weeks were given fermented milk containing Lactobacillus casei or placebo. NK cell activity in the peripheral blood mononuclear cells (PBMNC) was determined before and after the intake. Average number of cigarettes smoked and number of cigarettes that the subjects smoked before giving blood after getting up on the inspection day were asked, and these data were used to adjust the influence of smoking on NK cell activity. RESULTS: NK cell activity in individuals was inversely correlated to numbers of cigarettes smoked. Averaged NK cell activity adjusted by the numbers of cigarettes was significantly higher in individuals drinking fermented milk containing L. casei than those drinking a placebo. However, the proportion of NK cells was not different between individuals drinking either fermented milk containing L. casei or the placebo. CONCLUSIONS: Intake of fermented milk containing lactic acid bacteria was considered effective for restoring the NK cell activity of habitual smokers.

Adult↗
PubMed2004

IL-7 exacerbates chronic colitis with expansion of memory IL-7Rhigh CD4+ mucosal T cells in mice.

We have previously demonstrated that mucosal CD4(+) T cells expressing high levels of IL-7 receptor (IL-7R(high)) are pathogenic cells responsible for chronic colitis. Here we investigate whether IL-7 is directly involved in the expansion of IL-7R(high) memory CD4(+) mucosal T cells and the exacerbation of colitis. We first showed that CD4(+) lamina propria lymphocytes (LPLs) from wild-type, T cell receptor-alpha-deficient (TCR-alpha(-/-)), and recombinase-activating gene (RAG)-2(-/-)-transferred mice with or without colitis showed phenotypes of memory cells, but only CD4(+) LPLs from colitic mice showed IL-7R(high). In vitro stimulation by IL-7, but not by IL-15 and thymic stromal lymphopoietin, enhanced significant proliferative responses and survival of colitic CD4(+), but not normal CD4(+) LPLs. Importantly, in vivo administration of IL-7 mice accelerated the expansion of IL-7R(high) memory CD4(+) LPLs and thereby exacerbated chronic colitis in RAG-2(-/-) mice transferred with CD4(+) LPLs from colitic TCR-alpha(-/-) mice. Conversely, the administration of anti-IL-7R monoclonal antibody significantly inhibited the development of TCR-alpha(-/-) colitis with decreased expansion of CD4(+) LPLs. Collectively, the present data indicate that IL-7 is essential for the expansion of pathogenic memory CD4(+) T cells under pathological conditions. Therefore, therapeutic approaches targeting the IL-7R pathway may be feasible in the treatment of human inflammatory bowel disease.

Animals↗
PubMed2004

Modulation of Immune Functions by Foods.

Evidence is rapidly accumulating as to the beneficial effects of foods. However, it is not always clear whether the information is based on data evaluated impartially in a scientific fashion. Human research into whether foods modulate immune functions in either intervention studies or randomized controlled trials can be classified into three categories according to the physical state of subjects enrolled for investigation: (i) studies examining the effect of foods in healthy individuals; (ii) studies analyzing the effect of foods on patients with hypersensitivity; and (iii) studies checking the effect of foods on immunocompromized subjects, including patients who had undergone surgical resection of cancer and newborns. The systematization of reported studies has made it reasonable to conclude that foods are able to modulate immune functions manifesting as either innate immunity (phagocytic activity, NK cell activity) or acquired immunity (T cell response, antibody production). Moreover, improvement of immune functions by foods can normalize the physical state of allergic patients or cancer patients, and may reduce the risk of diseases in healthy individuals. Therefore, it is valuable to assess the immune-modulating abilities of foods by measuring at least one parameter of either innate or acquired immunity.

Journal Article↗
PubMed2004

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy.

Individual animals in the closed colony population of ddY mice were analyzed to clarify the major cause of age-dependent elevation of serum IgA and the appearance of human IgA nephropathy (IgAN)-like symptoms. Based on the serum IgA levels, the mice were classified into two subgroups. One was a high serum IgA group with some manifestations of IgAN through aging (ddY(High)), and the other was a normal serum IgA group without IgAN (ddY(Norm)). The ratio of urinary IgA to serum IgA was significantly reduced in ddY(High) mice, suggesting an impaired IgA clearance via secretion through the epithelial barrier. The actual clearance rate of the intravenously injected dimeric IgA in ddY(High) mice was found to be slower than that in ddY(Norm) mice. Furthermore, we found that the polymeric Ig receptors (pIgRs) that mediate transcytosis of IgA were poorly expressed in the glomeruli as well as in the intestine of ddY(High) mice, whereas the pIgRs were more abundantly expressed in ddY(Norm) mice. In addition, the comparative study using polymerase chain reaction showed that decreased pIgR expression occurred at the transcriptional level in the ddY(High) population. Taken together, these results suggest that a systemic defect in pIgR expression may result in impaired IgA secretion and accumulation of IgA in the serum of ddY(High) mice. The age-dependent changes of pIgR expression in the dimeric IgA secretion sites of ddY(High) mice suggest a possible cause for the elevation of serum IgA level and the pathogenesis of IgAN-like disease.

Aging↗
PubMed2002

Homeostatic regulation of intestinal villous epithelia by B lymphocytes.

The epithelial cell of the small intestine is one of the most rapidly regenerating cells in the body. However, the cellular mechanism and biological significance underlying this rapid regeneration remain elusive. In this study we examined the intestinal epithelia of mutant mice that lack B and/or T cells and those of normal littermates. The absence of B cells in Ig mu-chain mutant mice or B and T cells in recombination-activating gene (RAG)-2(-/-) as well as SCID mutant mice was associated with a marked acceleration of epithelial cell turnover and an up-regulation of the expression of MHC class II molecules. No such effects were observed in T cell-deficient TCR-delta and -beta double-mutant mice. As far as the goblet cells of villous epithelium are concerned, absolute numbers of them remained the same among these mutant mice that have no B and/or T cells. Alymphoplasia (aly/aly) mutant mice that lacked Peyer's patches and Ig-producing cells in the lamina propria, but harbored a large number of intestinal mucosal T cells, also displayed a significant acceleration of epithelial cell turnover and, to some extent, up-regulated expression of MHC class II molecules. Notably, the accelerated epithelial cell turnover was not observed and returned to normalcy in the Ig mu-chain mutant mice that had been given antibiotic-containing water. These findings indicate that B cells down-regulate the generation and differentiation of intestinal epithelial cells in the normal wild-type condition and suggest that enteric microorganisms are implicated in the accelerated generation of epithelial cells in mice that have no B cells.

Ampicillin↗
PubMed2002

Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines.

The role of secretory IgA in conferring cross-protective immunity was examined in polymeric (p)IgR knockout (KO) mice immunized intranasally with different inactivated vaccines prepared from A/PR/8/34 (H1N1), A/Yamagata/120/86 (H1N1), A/Beijing/262/95 (H1N1), and B/Ibaraki/2/85 viruses and infected with the A/PR/8/34 virus in the upper respiratory tract (RT)-restricting volume. In wild-type mice, immunization with A/PR/8/34 or its variant (A/Yamagata/120/86 and A/Beijing/262/95) vaccines conferred complete protection or partial cross-protection against infection, while the B-type virus vaccine failed to provide protection. The protection or cross-protection was accompanied by an increase in the nasal A/PR/8/34 hemagglutinin-reactive IgA concentration, which was estimated to be >30 times the serum IgA concentration and much higher than the nasal IgG concentration. In contrast, the blockade of transepithelial transport of dimeric IgA in pIgR-KO mice reduced the degree of protection or cross-protection, in parallel with the marked increase in serum IgA concentration and the decrease in nasal IgA concentration (about 20 and 0.3 times those in wild-type mice, respectively). The degree of the reduction of protection or cross-protection was moderately reversed by the low but non-negligible level of nasal IgA, transudates from the accumulated serum IgA. These results, together with the absence of the IgA-dependent cross-protection in the lower RT and the unaltered level of nasal or serum IgG in wild-type and pIgR-KO mice, confirm that the actively secreted IgA plays an important role in cross-protection against variant virus infection in the upper RT, which cannot be substituted by serum IgG.

Adjuvants, Immunologic↗
PubMed2002

Inhibition of B16 melanoma experimental metastasis by interferon-gamma through direct inhibition of cell proliferation and activation of antitumour host mechanisms.

Interferon-gamma (IFN-gamma) has pleiotropic activities other than its antivirus action, including cell growth inhibition, natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activation, and angiogenesis inhibitory activity, and these activities are supposed to be involved in its antitumour activity. However, it has not been completely elucidated which activity is mainly involved in the tumour suppression in vivo. In this study, we analysed inhibitory mechanisms of endogenous IFN-gamma against B16 melanoma experimental metastasis. After intravenous injection of tumour cells, tumour deposits in the lungs and liver were increased and life span was shorter in IFN-gamma(-/-) mice, indicating important roles for IFN-gamma in antitumour mechanisms. Interestingly, tumour deposits were not increased in IFN-gamma receptor (R)(-/-) mice. Furthermore, only low levels of cell-mediated immunity against the tumour and activation of NK cells were observed, indicating that antimetastatic effects of IFN-gamma is not mediated by host cells. The survival period of B16 melanoma-bearing IFN-gamma R(-/-) mice was, however, shorter than wild-type mice. These observations suggest that IFN-gamma prevents B16 melanoma experimental metastasis by directly inhibiting the cell growth, although antitumour host functions may also be involved in a later phase.

Animals↗