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Yukino Kimura

Publications and source records attributed to Yukino Kimura.

4 recordsLinked to original sources
PubMed2005

Development of murine plasmacytoid dendritic cells defined by increased expression of an inhibitory NK receptor, Ly49Q.

Plasmacytoid dendritic cells (PDCs) are defined in mice by a unique combination of markers: CD11c, B220, and Ly6C/G. We have reported previously that PDCs express Ly49Q, a lectin-type killer cell inhibitory receptor. We now find that different expression levels of Ly49Q define sequential developmental stages of PDCs in bone marrow. Although PDCs in spleen and lymph nodes express high levels of Ly49Q, a significant portion of CD11c(+)B220(+) PDCs in bone marrow lack Ly49Q, as well as the CD4 and MHC II. Purified Ly49Q(-) marrow PDCs spontaneously up-regulate Ly49Q after overnight culture without cell proliferation and acquire most features of typical PDCs in spleen. When exposed to TLR ligands, such as CpG-oligodeoxynucleotide and hemagglutinating virus of Japan (Sendai virus), Ly49Q(-) PDCs increase CD86 and MHC class II expression but produce less IFN-alphabeta, IL-6, and IL-12p70 than Ly49Q(+) PDCs, although they are able to produce comparable amounts of TNF-alpha. However, interestingly, Ly49Q(-) PDCs do not produce TNF-alpha in response to the TLR2 ligand, Pam3SCK(4), whereas Ly49Q(+) PDCs did. Therefore, Ly49Q is a new marker to identify a precursor form of PDCs that participates in innate immunity.

Animals↗
PubMed2004

Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins.

The mouse (m) DC-SIGN family consists of several homologous type II transmembrane proteins located in close proximity on chromosome 8 and having a single carboxyl terminal carbohydrate recognition domain. We first used transfected non-macrophage cell lines to compare the polysaccharide and microbial uptake capacities of three of these lectins--DC-SIGN, SIGNR1 and SIGNR3--to another homologue mLangerin. Each molecule shares a potential mannose-recognition EPN-motif in its carbohydrate recognition domain. Using an anti-Tag antibody to follow Tag-labeled transfectants, we found that each molecule could be internalized, although the rates differed. However, mDC-SIGN was unable to take up FITC-dextran, FITC-ovalbumin, zymosan or heat-killed Candida albicans. The other three lectins showed distinct carbohydrate recognition properties, assessed by blocking FITC-dextran uptake at 37 degrees C and by mannan binding activity at 4 degrees C. Furthermore, only SIGNR1 was efficient in mediating the capture by transfected cells of Gram-negative bacteria, such as Escherichia coli and Salmonella typhimurium, while none of the lectins tested were competent to capture Gram-positive bacteria, Staphylococcus aureus. Interestingly, transfectants with SIGNR1 lacking the cytoplasmic domain were capable of binding FITC-zymosan in a manner that was abolished by EDTA or mannan, but not laminarin. In addition, resident peritoneal CD11b+ cells expressing SIGNR1 bound zymosan at 4 degrees C in concert with a laminarin-sensitive receptor. Therefore these homologous C-type lectins have distinct recognition patters for microbes despite similarities in the carbohydrate recognition domains.

Animals↗
PubMed2002

Immune tolerance after delivery of dying cells to dendritic cells in situ.

Peripheral immune tolerance is believed to be induced by the processing and presentation of self-tissues that die during physiologic tissue turnover. To examine the mechanism that mediates tolerance, we injected mice with dying syngeneic TAP(-/-) splenocytes loaded with small amounts of the protein antigen, ovalbumin (OVA). After ingestion and presentation of cell-associated OVA by the CD8(+) subset of dendritic cells in situ, large numbers of antigen-reactive, CD8(+) T cell receptor (TCR) transgenic T lymphocytes were driven into cell cycle, but then the T cells were deleted. The animals were also tolerant to challenge with OVA in complete Freund's adjuvant. An agonistic anti-CD40 monoclonal antibody was then administered together with the OVA-loaded splenocytes, so that the dendritic cells in the recipient mice would mature. In contrast to observations made in the steady state, the antigen-reactive T cells expanded in numbers for 1-2 wk and produced large amounts of interleukin 2 and interferon gamma, while the animals retained responsiveness to antigen rechallenge. The specific tolerance that develops when dendritic cells process self tissues in the steady state should prevent or reduce the development of autoimmunity when dying cells are subsequently processed during infection.

Adoptive Transfer↗