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  • The American Association of Immunologists  (14)
  • 1
    Online Resource
    Online Resource
    The Role of the Basic Helix-Loop-Helix Transcription Factor Dec1 in the Regulatory T Cells
    The American Association of Immunologists ; 2010
    In:  The Journal of Immunology Vol. 185, No. 12 ( 2010-12-15), p. 7330-7339
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 185, No. 12 ( 2010-12-15), p. 7330-7339
    Abstract: Naturally occurring regulatory T (Treg) cells play a central role in the maintenance of immune homeostasis and in restraining the development of spontaneous inflammatory responses. However, the underlying mechanisms of Treg homeostasis remain incompletely understood. Of particular note, the IL-2Rα (CD25) is crucial for the homeostasis of Treg cells and the prevention of lymphoproliferative autoimmune disease. In this paper, we report that the basic helix-loop-helix transcription factor Dec1 is involved in the homeostasis of Treg cells and plays a role in their survival or expansion after adoptive transfer to lymphopenic recipients. Hence, it is crucial for the suppression of effector T cell-mediated inflammatory responses. Enforced expression of Dec1 upregulates CD25 expression during thymocyte development and increases the number of Treg cells in the periphery. Dec1 binds the transcription factor Runx1 and colocalizes with Runx1 in Treg cells. Specifically, we demonstrate that in Treg cells the Dec1/Runx1 complex binds to regulatory elements present in the Il-2rα locus. Collectively, these data show how Dec1 mechanistically acts in Treg cells.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1001381
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2010
    detail.hit.zdb_id: 1475085-5
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  • 2
    Online Resource
    Online Resource
    Caspase-Independent Cell Death by CD300LF (MAIR-V), an Inhibitory Immunoglobulin-Like Receptor on Myeloid Cells
    The American Association of Immunologists ; 2008
    In:  The Journal of Immunology Vol. 180, No. 1 ( 2008-01-01), p. 207-213
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 180, No. 1 ( 2008-01-01), p. 207-213
    Abstract: The myeloid-associated Ig-like receptor family (CD300) consists of nine activating or inhibitory cell surface receptors preferentially expressed on myeloid cells and are encoded by the genes in a small cluster on mouse chromosome 11. One of the receptors, CD300LF (MAIR-V), has a long cytoplasmic tail containing two consensus ITIMs and an immunoreceptor tyrosine-based switching motif, suggesting that CD300LF regulates the activation of myeloid cells. However, the functional characteristics of this receptor are still incompletely understood. In this study, we demonstrate that cross-linking CD300LF with anti-CD300LF mAb induced cell death in peritoneal macrophages as well as in several transfectants expressing CD300LF. CD300LF-mediated cell death was dependent on the cytoplasmic region but did not require an ITIM or immunoreceptor tyrosine-based switching motif. Scanning electron microscopy revealed a loss of blebs from the surface of the dead cells mediated by CD300LF, a morphological feature similar to that observed in apoptotic cells. However, CD300LF-mediated cell death was not inhibited by a caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, or autophagy inhibitors, 3-methyladenine or N-acetyl-l-cystein. Moreover, the splicing isoform of a transcription factor, X-box binding protein-1, which is produced in dead cells as a response to endoplasmic reticulum stress, was not detected. Together, these results indicate that CD300LF mediates caspase and endoplasmic reticulum stress-independent cell death by a novel mechanism.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.180.1.207
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2008
    detail.hit.zdb_id: 1475085-5
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  • 3
    Online Resource
    Online Resource
    Differential Involvement of Src Family Kinases in Fcγ Receptor-Mediated Phagocytosis
    The American Association of Immunologists ; 2000
    In:  The Journal of Immunology Vol. 165, No. 1 ( 2000-07-01), p. 473-482
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 165, No. 1 ( 2000-07-01), p. 473-482
    Abstract: The tyrosine phosphorylation cascade originated from Fcγ receptors (FcγRs) is essential for macrophage functions including phagocytosis. Although the initial step is ascribed to Src family tyrosine kinases, the role of individual kinases in phagocytosis signaling is still to be determined. In reconstitution experiments, we first showed that expression in the RAW 264.7 cell line of C-terminal Src kinase (Csk) inhibited and that of a membrane-anchored, gain-of-function Csk abolished the FcγR-mediated signaling that leads to phagocytosis in a kinase-dependent manner. We next tested reconstruction of the signaling in the membrane-anchored, gain-of-function Csk-expressing cells by introducing Src family kinases the C-terminal negative regulatory sequence of which was replaced with a c-myc epitope. Those constructs derived from Lyn and Hck (a-Lyn and a-Hck) that associated with detergent-resistant membranes successfully reconstructed FcγR-mediated Syk activation, filamentous actin rearrangement, and phagocytosis. In contrast, c-Src-derived construct (a-Src), that was excluded from detergent-resistant membranes, could not restore the series of phagocytosis signaling. Tyrosine phosphorylation of Vav and c-Cbl was restored in common by a-Lyn, a-Hck, and a-Src, but FcγRIIB tyrosine phosphorylation, which is implicated in negative signaling, was reconstituted solely by a-Lyn and a-Hck. These findings suggest that Src family kinases are differentially involved in FcγR-signaling and that selective kinases including Lyn and Hck are able to fully transduce phagocytotic signaling.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.165.1.473
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2000
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  • 4
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    Online Resource
    Microbial enzyme stereoselectively converts EPA into 17( S ),18( R )-epoxyeicosatetraenoic acid useful for the amelioration of contact hypersensitivity
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 1_Supplement ( 2020-05-01), p. 83.22-83.22
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 83.22-83.22
    Abstract: Dietary intake of ω3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are beneficial for health control because ω3 fatty acids are metabolized to pro-resolution and anti-inflammatory lipid metabolites. We previously identified 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) as a new lipid metabolite endogenously generated from EPA that exhibits potent anti-allergic and anti-inflammatory properties. However, the chemically synthesized 17,18-EpETE is enantiomeric mixture concerning to its epoxy group, i.e., 17(S),18(R)-EpETE and 17(R),18(S)-EpETE, and the stereostructural differences in anti-inflammatory effect of 17,18-EpETE has not been clarified. Because it is necessary to identify which isomer shows physiological function to develop it as a medicine, we evaluated stereospecific effects of 17(S),18(R)-EpETE and 17(R),18(S)-EpETE in amelioration of skin contact hypersensitivity. As a result, we found that anti-inflammatory activity was detected in 17(S),18(R)-EpETE, but not 17(R),18(S)-EpETE. In addition, we found that cytochrome P450 BM-3 derived from Bacillus megaterium stereoselectively converts EPA into 17(S),18(R)-EpETE, which effectively inhibited the development of contact hypersensitivity by inhibiting neutrophil migration in a G protein-coupled receptor 40-dependent manner. These results demonstrated that immune cells (e.g., neutrophils) distinguish biological active lipid metabolites stereoselectively for the control of their activity, which is a new strategy for the development of efficient immunotherapy.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.204.Supp.83.22
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    Control of Germinal Center Reaction against T-Independent Antigens by the Fc(alpha)/(mu)Receptor (53.7)
    The American Association of Immunologists ; 2007
    In:  The Journal of Immunology Vol. 178, No. 1_Supplement ( 2007-04-01), p. S104-S105
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 178, No. 1_Supplement ( 2007-04-01), p. S104-S105
    Abstract: Germinal center (GC) formation in the secondary lymphoid follicles is induced by immunization with T-independent (TI) as well as T-dependent (TD) antigens. However, structural and functional characteristics of the GC induced by TI antigens have not been elucidated. Here, we show that marginal zone B (MZB) cells and follicular dendritic cells (FDC) preferentially express the Fc receptor for IgM and IgA (Fc(alpha)/(mu)R) as well as the complement receptor CD21/35. Mice deficient in Fc(alpha)/(mu)R showed significantly enhanced GC formation in response to TI antigens, in which both B cells and FDC were involved. Fc(alpha)/(mu)R-deficient mice also showed enhanced TI antigen retention by MZB cells and FDC, CXCL13 expression and affinity maturation of IgG3. Depletion of complements by injection with cobra venom factor completely abrogated this phenotype. These results suggest that Fc(alpha)/(mu)R controls GC reactions and affinity maturation of antibodies against TI antigens by interacting with complement cascades.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.178.Supp.53.7
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2007
    detail.hit.zdb_id: 1475085-5
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  • 6
    Online Resource
    Online Resource
    Cloning and Characterization of the Homolog of Mammalian Lipopolysaccharide-Binding Protein and Bactericidal Permeability-Increasing Protein in Rainbow Trout Oncorhynchus mykiss
    The American Association of Immunologists ; 2002
    In:  The Journal of Immunology Vol. 168, No. 11 ( 2002-06-01), p. 5638-5644
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 168, No. 11 ( 2002-06-01), p. 5638-5644
    Abstract: We cloned two cDNAs denoted as RT-LBP/BPI-1 and RT-LBP/BPI-2, respectively, which were derived from the mRNA of head kidney from rainbow trout. They showed structural homology with LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) in mammals. The full-length cDNA of RT-LBP/BPI-1 and RT-LBP/BPI-2 is 1666 and 1741 bp, respectively. Both cDNAs encoded 473 aa residues, including the amino acids conserved in mammalian LBP and BPI proteins that were assumed to be involved in LPS binding. The overall coding sequence of RT-LBP/BPI-1 has 33% amino acid homology to human LBP and 34% to human BPI, and RT-LBP/BPI-2 has 32% amino acid homology to human LBP and 33% to human BPI. Three-dimensional structure analysis by three-dimensional/one-dimensional (3D-1D) methods also demonstrated that RT-LBP/BPI-1 and RT-LBP/BPI-2 proteins showed significant similarity to human BPI, having a boomerang shape with N-terminal and C-terminal barrels. Phylogenetic analysis showed that the LBP and BPI genes seemed to be established after the divergence of mammals from teleosts. These results suggested that RT-LBP/BPI-1 and RT-LBP/BPI-2 may be a putative ortholog for mammalian LBP and/or BPI genes. This is the first study to identify the LBP family genes from nonmammalian vertebrates.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.168.11.5638
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2002
    detail.hit.zdb_id: 1475085-5
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  • 7
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    Online Resource
    CD155 (PVR/Necl5) Mediates a Costimulatory Signal in CD4+ T Cells and Regulates Allergic Inflammation
    The American Association of Immunologists ; 2015
    In:  The Journal of Immunology Vol. 194, No. 12 ( 2015-06-15), p. 5644-5653
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 12 ( 2015-06-15), p. 5644-5653
    Abstract: Although Th1 and Th2 cells are known to be involved in allergic inflammatory diseases, the molecular mechanisms underlying their differentiation are incompletely understood. In this study, we identified CD155 as a costimulatory molecule on CD4+ T cells. Importantly, CD155-mediated signaling induced Th1 development in both humans and mice, as evidenced by production of IFN-γ and upregulation of Tbx21 transcription; these effects were independent of IL-12 but dependent on NF-κB–induced autocrine IFN-γ that triggered positive feedback via STAT1 activation. Mice genetically deficient in CD155 or treated with anti-CD155 Ab exhibited attenuated Th1-type contact hypersensitivity. Thus, CD155 plays an important regulatory role in helper T cell differentiation and allergic diseases.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1401942
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2015
    detail.hit.zdb_id: 1475085-5
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  • 8
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    Online Resource
    Cutting Edge: Identification of Marginal Reticular Cells as Phagocytes of Apoptotic B Cells in Germinal Centers
    The American Association of Immunologists ; 2018
    In:  The Journal of Immunology Vol. 200, No. 11 ( 2018-06-01), p. 3691-3696
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 11 ( 2018-06-01), p. 3691-3696
    Abstract: Germinal centers (GCs) in secondary lymphoid organs generate large numbers of apoptotic B cells that must be eliminated by phagocytes to prevent the development of autoimmune diseases. Although tingible body macrophages engulf apoptotic GC B cells, whether stromal cells are also involved in this process is unclear. In this study, we identified marginal reticular cells (MRCs) as novel nonprofessional phagocytes for the clearance of apoptotic GC B cells in the spleen. We used CD19eGFP (CD19creZ/EG) mice, which express enhanced GFP (eGFP) under the control of CD19cre expression, to track B cells in the GCs after immunization with NP-chicken γ globulin plus aluminum salt. We demonstrated that the MRC population, as determined by expression of podoplanin or Rankl, specifically showed an eGFP signal in the cytoplasm after immunization. These results suggest that MRCs contribute to the clearance of apoptotic B cells in GCs.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1701293
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2018
    detail.hit.zdb_id: 1475085-5
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  • 9
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    Online Resource
    Spatial Raft Coalescence Represents an Initial Step in FcγR Signaling
    The American Association of Immunologists ; 2002
    In:  The Journal of Immunology Vol. 169, No. 1 ( 2002-07-01), p. 193-203
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 169, No. 1 ( 2002-07-01), p. 193-203
    Abstract: Characterization of lipid rafts as separated membrane microdomains consist of heterogeneous proteins suggesting that lateral assembly of rafts after Ag receptor cross-linking represents the earliest signal generating process. In line with the concept, cross-linked Ag receptors have been shown to associate with detergent-insoluble raft fraction without the aid of Src family kinases. However, it has not been established whether spatial raft coalescence could also precede Src family kinase activation. In this study, we showed that spatial raft coalescence after low-affinity FcγR cross-linking in RAW264.7 macrophages is independent of Src family kinase activity. The lateral raft assembly was found to be ascribed to the action of ligand-binding subunits, rather than to immunoreceptor tyrosine-based activation motif-bearing signal subunits, because monomeric murine FcγRIIb expressed in rat basophilic leukemia cells successfully induced spatial raft reorganization after cross-linking. We also showed that extracellular and transmembrane region of FcγRIIb is sufficient for raft stabilization. Moreover, this receptor fragment triggers rapid calcium mobilization and linker for activation of T cells phosphorylation, in a manner sensitive to Src family kinase inhibition and to cholesterol depletion. Presence of immunoreceptor tyrosine-based inhibitory motif and addition of immunoreceptor tyrosine-based activation motif to the receptor fragment abolished and enhanced the responses, respectively, but did not affect raft stabilization. These findings support the concept that ligand-binding subunit is responsible for raft coalescence, and that this event triggers initial biochemical signaling.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.169.1.193
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2002
    detail.hit.zdb_id: 1475085-5
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  • 10
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    Online Resource
    Enhanced humoral immune responses against T-independent antigens in Fcα/μR-deficient mice (39.14)
    The American Association of Immunologists ; 2009
    In:  The Journal of Immunology Vol. 182, No. 1_Supplement ( 2009-04-01), p. 39.14-39.14
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 1_Supplement ( 2009-04-01), p. 39.14-39.14
    Abstract: IgM is an antibody class common to all vertebrates that plays a primary role in host defences against infection. Binding of IgM with an antigen initiates the complement cascade, accelerating cellular and humoral immune responses. However, the functional role of the Fc receptor for IgM in such immune responses remains obscure. Here we show that mice deficient in Fcα/μR, an Fc receptor for IgM expressed on B cells and follicular dendritic cells (FDCs), had enhanced germinal center formation and affinity maturation and memory induction of IgG3+ B cells after immunization with T-independent (TI) antigens. Moreover, Fcα/μR-deficient mice showed prolonged antigen retention by marginal zone B (MZB) cells and FDCs. In vitro studies demonstrated that interaction of the IgM immune complex with Fcα/μR partly suppressed TI antigen retention by MZB cells. We further showed that downregulation of complement receptor (CR)1 and CR2 or complement deprivation by in vivo injection with anti-CR1/2 antibody or cobra venom factor attenuated antigen retention by MZB cells and GC formation after immunization with TI antigens in Fcα/μR-/-_mice. Taken together, these results suggest that Fcα/μR negatively regulates TI antigen retention by MZB cells and FDCs, leading to suppression of humoral immune responses against T-independent antigens.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.182.Supp.39.14
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2009
    detail.hit.zdb_id: 1475085-5
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