Little is known about the mechanism of tissue maintenance and regeneration for lingual epithelial cells. And specific stem cell markers of the lingual epithelium and the function have not much been reported so far. Multicolor lineage tracing method enables to distinguish the cell clusters derived from many different stem cells and clarifies the area derived from the long-term stem cells. Then in the area, we identify a single Bmi1 positive cell as specific lingual stem cells. By Bmi1-positive cells lineage tracing, for the first time we shows Bmi1-positive stem cells have maintained the lingual epithelium for long time and that can regenerate the injured lingual tissues.
The Sox2 protein is a transcription factor and a member of the SoxB1 family. The distribution and functions of Sox2 have been well studied in neural stem cells of the central nervous system (CNS). In the neural stem cells of the CNS, the Sox2 protein helps to maintain the stem cell state. Some recent reports have shown that the Sox2 gene is also expressed in the cells of the peripheral nervous system (PNS) throughout life. During PNS development, the Sox2 protein regulates the epithelial-to-mesenchymal transition, neurogenesis and myelination. In the adult PNS, our recent reports using immunohistochemistry showed that Sox2 is found in some types of rat glial cells and promotes satellite glial cell survival. This review outlines the distribution and functions of Sox2 in the PNS.
Dendritic cells (DCs) are initiators of innate immunity and acquired immunity through the production of cytokines such as interferon-α (IFN-α) and interleukin-12 (IL-12). Nucleic acids (DNA, RNA) from damaged cells or pathogens are important activators not only for anti-microbial innate immune responses but also in the pathogenesis of autoimmune diseases. Plasmacytoid DCs are regarded as the main effectors for the nucleic acids-mediated innate immunity by possessing toll-like receptor 9 (TLR9). We here found that double-stranded DNA (dsDNA) complexed with lipotransfectants triggered activation of human monocyte-derived DCs (monoDCs), leading to the preferential production of IFN-α but not IL-12. This indicates that myeloid DCs also function as supportive effectors against the invasion of pathogenic microbes through the DNA-mediated activation in innate immunity. The dsDNA with lipotransfectants can be taken up by monoDCs without co-localization of endosomal LAMP1 staining, and the dsDNA-mediated IFN-α production was not impaired by chloroquine. These findings indicate that monoDC activation by dsDNA does not involve the endosomal TLR pathway. In contrast, single-stranded RNA (ssRNA) stimulated monoDCs to secrete IL-12 but not IFN-α. This process was inhibited by chloroquine, suggesting an involvement of the TLR pathway in ssRNA-mediated monoDC activation. As might be inferred from our findings, monoDC may function as a traffic control between innate immunity via IFN-α production and acquired immunity via IL-12 production, depending on the type of nucleic acids. Our results provide a new insight into the biological action of monoDC underlying the dsDNA-mediated activation of protective or pathogenic immunity.
Plasmacytoid dendritic cells (PDCs) have a potential to prime naïve CD4+ T cells to differentiate into IL-10-producing T regulatory cells through inducible costimulatory ligand (ICOS-L), which has been implicated in the induction of T regulatory cell-mediated peripheral tolerance. Although PDCs in response to TLR-stimuli show a functional property not only to upregulate ICOS-L but also to produce a large amount of type I IFNs and proinflammatory cytokines TNF and IL-6, the role of these cytokines in T cell priming has remained elusive. Therefore, we here investigate functional involvement of PDC-derived cytokines in the generation of IL-10-producing T regulatory cells through ICOS-L. We cultured naïve and memory CD4+ T cells with anti-CD3 mAbs in the presence or absence of ICOS-L-transfected L cells for 5 to 7 days. Addition of IFN-α to the T cell culture enhanced the ICOS-L-mediated generation of IL-10-producing T cells from both naïve and memory CD4+ T cells. However, IL-10 production in T cells was not significantly increased by IFN-α single stimulation. Thus, type I IFNs act as a supplementary factor for the IL-10 production during T cell polarization. We also found that PDC-derived TNF-α contributed to the induction of ICOS-L expression on PDCs in an autocrine manner. In addition, PDC-derived IL-6 induced ICOSL-mediated IL-10-producing T cell generation under Th2 condition. However, ICOS-L, type I IFNs, and IL-6 under Th2 condition did not induce FOX-P3 expression on T cells. Our results suggest that PDC-derived cytokines, TNF, IL-6, and Type I IFNs play a complementary role for the generation of IL-10-producing T cells through ICOSL, which may contributes to peripheral tolerance for controlling an excessive immune response.
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