PubMed Health⌕ Search

Biomedical subjects

Tomonori Nochi

Publications and source records attributed to Tomonori Nochi.

6 recordsLinked to original sources

Innate immunity in the mucosal immune system.

The mucosal immune system is equipped with unique innate and acquired defense mechanisms which provide a first line of protection against ingested and inhaled infectious agents. Peyer's patches (PPs) and nasopharynx-associated lymphoid tissue (NALT) have been shown to be important inductive sites for the initiation of the acquired phase of antigen-specific immune responses. In addition, the mucosal innate immune system acts as both a physical and an immunological boundary, playing a key role in the sensing and eliminating of pathogens and in the creating of symbiosis. The mucus layer covering the mucosal epithelium acts as a first physical and biochemical barrier. An additional layer of physical protection against microorganisms is provided by a tightly interlaced cell-to-cell network of epithelial cells and intraepithelial lymphocytes. Various antimicrobial peptides produced by the epithelium and secreted into the mucosal lumen can directly kill the invading pathogenic bacteria. Finally, Toll-like receptors (TLRs) associated with the mucosal compartment have been shown to recognize the pathogen-associated molecular patterns (PAMPs) of a variety of pathogenic and commensal microorganisms. Therefore, a greater understanding of the immunological progression from mucosal innate to acquired immune systems should facilitate the development of new generation of mucosal vaccines to prevent and control infectious diseases.

Animals↗

Localization of interleukin-18 and its receptor in somatotrophs of the bovine anterior pituitary gland.

A pro-inflammatory cytokine, interleukin 18 (IL-18), induces intracellular expression of IL-1 and the release of IL-6. IL-1 and IL-6 has been detected in anterior pituitary cells, suggesting that IL-18 is produced in anterior pituitary cells and may serve to aid immuno-endocrine regulation. In the present study, we addressed this hypothesis by investigating the intracellular localization of IL-18 and its receptor in bovine anterior pituitary gland. IL-18 mRNA and its protein were detected in the anterior pituitary gland by RT-PCR and Western blotting. In situ hybridization showed that IL-18 mRNA was expressed in the anterior pituitary cells. Immunohistochemistry of IL-18 and specific hormones revealed the presence of IL-18 in somatotrophs. Furthermore, the expression of GH mRNA in IL-18 immunoreactive cells was confirmed by immuno-laser microdissection. These results first demonstrated that somatotrophs produced IL-18. Subsequently, the distribution of the IL-18 receptor alpha (IL-18Ralpha) was investigated in order to understand IL-18 signaling among the anterior pituitary cells. Bovine IL-18Ralpha cDNA was partially sequenced and detected in the anterior pituitary gland by RT-PCR. Immunohistochemistry of IL-18Ralpha, IL-18 and GH showed that IL-18Ralpha was co-localized in IL-18 immunoreactive cells or somatotrophs. These data suggest that IL-18 acts on somatotrophs as an immuno-endocrine mediator through the autocrine pathway.

Amino Acid Sequence↗

Intracellularly expressed TLR2s and TLR4s contribution to an immunosilent environment at the ocular mucosal epithelium.

Epithelial cells are key players in the first line of defense offered by the mucosal immune system against invading pathogens. In the present study we sought to determine whether human corneal epithelial cells expressing Toll-like receptors (TLRs) function as pattern-recognition receptors in the innate immune system and, if so, whether these TLRs act as a first line of defense in ocular mucosal immunity. Incubation of human primary corneal epithelial cells and the human corneal epithelial cell line (HCE-T) with peptidoglycan or LPS did not lead to activation, at the level of DNA transcription, of NF-kappaB or the secretion of inflammation-associated molecules such as IL-6, IL-8, and human beta-defensin-2. However, when incubated with IL-1alpha to activate NF-kappaB, the production by these cells of such inflammatory mediators was enhanced. Human corneal epithelial cells were observed to express both TLR2- and TLR4-specific mRNA as well as their corresponding proteins intracellularly, but not at the cell surface. However, even when LPS was artificially introduced into the cytoplasm, it did not lead to the activation of epithelial cells. Taken together, our results demonstrate that the intracellular expression of TLR2 and TLR4 in human corneal epithelial cells fails to elicit innate immune responses and therefore, perhaps purposely, contributes to an immunosilent environment at the ocular mucosal epithelium.

Cornea↗

Intestinal villous M cells: an antigen entry site in the mucosal epithelium.

M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be the principal sites for the sampling of gut luminal antigens. Thus, PP have long been considered the gatekeepers of the mucosal immune system. Here, we report a distinct gateway for the uptake of gut bacteria: clusters of non-follicle-associated epithelium-associated Ulex europaeus agglutinin (UEA)-1(+) cells, which we have designated intestinal villous M cells. Interestingly, villous M cells are developed in various PP [or gut-associated lymphoid tissue (GALT)]-null mice, such as in utero lymphotoxin beta receptor (LTbetaR)-Ig-treated, lymphotoxin alpha (LTalpha)(-/-), tumor necrosis factor/LTalpha(-/-), and inhibition of differentiation 2 (Id2)(-/-) mice. Intestinal villous M cells have been observed to take up GFP-expressing Salmonella, Yersinia, and Escherichia coli-expressing invasin, as well as gut bacterial antigen for subsequent induction of antigen-specific immune responses. Thus, the identified villous M cells could be an alternative and PP-independent gateway for the induction of antigen-specific immune responses by means of the mucosal compartment.

Animals↗

Biological role of Ep-CAM in the physical interaction between epithelial cells and lymphocytes in intestinal epithelium.

The mucosal epithelium including intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) provide a first line of defense in the gastrointestinal tract. However, limited information is currently available concerning the nature of the physical interaction molecule that interconnects IECs and IELs. Among the several monoclonal antibodies (mAbs) generated by immunizing porcine IECs, mAb (5-15-1) was shown to strongly react with IELs in addition to IECs. MALDI-TOF-MS and tandem MS analysis suggested that the antigen belongs to a family of human homophilic epithelial cell adhesion molecule (Ep-CAM). The amino acid sequence of porcine Ep-CAM showed 82.8%, 78.1%, and 76.8% homology compared to human, mouse, and rat Ep-CAM. Moreover, 5-15-1 specifically reacted with transfectant of porcine Ep-CAM. These data suggest that the Ep-CAM may act as a physical homophilic interaction molecule between IELs and IECs at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection.

Amino Acid Sequence↗