A5021144595- Immune Cell Function and Interaction
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immune cells in cancer
- Virus-based gene therapy research
- Inflammation biomarkers and pathways
- Immunotherapy and Immune Responses
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Respiratory Support and Mechanisms
- Systemic Lupus Erythematosus Research
- Diabetes and associated disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Adhesion Molecules Research
- interferon and immune responses
- NF-κB Signaling Pathways
- Inflammasome and immune disorders
- Monoclonal and Polyclonal Antibodies Research
- Protease and Inhibitor Mechanisms
- Acute Myeloid Leukemia Research
- Cytomegalovirus and herpesvirus research
University of Washington
2016-2025
Virginia Mason Medical Center
2009-2024
Benaroya Research Institute
2015-2024
Seattle University
2023
University of Münster
2011
Cancer Research Institute
2002-2006
University of California, San Francisco
2002-2005
Howard Hughes Medical Institute
1997-1998
University of Bristol
1998
Novartis (Switzerland)
1993-1995
Abstract DAP12 is an ITAM-containing adapter that associates with receptors in myeloid and NK cells. DAP12-associated can give activation signals leading to cytokine production; however, some situations, inhibits production stimulated through TLRs FcRs. Here we show Triggering Receptor Expressed on Myeloid cells (TREM)-2 responsible for the DAP12-mediated inhibition mouse macrophages. A chimeric receptor composed of extracellular domain TREM-2 cytoplasmic inhibited TLR- FcR-induced TNF...
Natural killer (NK) cells play a critical role in the innate immune response against cytomegalovirus (CMV) infections. Although CMV encodes several gene products committed to evasion of adaptive immunity, viral modulation NK cell activity is only beginning be appreciated. A previous study demonstrated that mouse m152-encoded gp40 glycoprotein diminished expression ligands for activating receptor NKG2D on surface virus-infected cells. Here we have defined precise are affected and directly...
Phagocytosis, which is essential for the immune response to pathogens, initiated by specific interactions between pathogens and cell surface receptors expressed phagocytes. This study identifies triggering receptor on myeloid cells 2 (TREM-2) its signaling counterpart DAP12 as a molecular complex that promotes phagocytosis of bacteria. Expression TREM-2–DAP12 enables nonphagocytic Chinese hamster ovary internalize function depends actin cytoskeleton dynamics activity small guanosine...
Macrophages recognize the presence of infection by using Toll-like receptor (TLR) family proteins that detect ligands on bacterial, viral, and fungal pathogens. We show murine macrophages stimulated with pathogen products known to signal through TLRs express for NKG2D receptor, found NK cells, activated CD8(+) T cells macrophages. TLR signaling, MyD88 adaptor, up-regulates transcription retinoic acid early inducible-1 (RAE-1) ligands, but not H-60 or UL16-binding protein-like transcript-1....
Abstract Tumors often escape immune-mediated destruction by suppressing lymphocyte infiltration or effector function. New approaches are needed that overcome this suppression and thereby augment the tumoricidal capacity of tumor-reactive lymphocytes. The cytokine interleukin-15 (IL-15) promotes proliferation CD8+ T cells, natural killer (NK) NKT cells; however, it has a short half-life high doses to achieve functional responses in vivo. biological activity IL-15 can be dramatically increased...
Abstract DCs play a key role in defense against infections and also preventing inflammatory autoimmune diseases. The response of to pathogens is tightly regulated by many mechanisms allow for appropriate, but not pathogenic, responses. We previously showed that with deficiencies two ITAM‐bearing signaling adapters, DAP12 FcRγ, produce more cytokines upon treatment Toll‐like receptor (TLR) agonists than WT DCs. Here, we investigated whether the TREM‐2 pairs inhibit TLR responses...
Background— S100A9 is constitutively expressed in neutrophils, dendritic cells, and monocytes; associated with acute chronic inflammatory conditions; implicated obesity cardiovascular disease humans. Most of the secreted derived from myeloid cells. A recent report demonstrated that mice deficient exhibit reduced atherosclerosis compared controls suggested this effect was due large part to loss bone marrow–derived Methods Results— To directly investigate role insulin resistance mice,...
Fluorescence can be harnessed to monitor microbial fate and investigate functional outcomes of individual cell-host cell encounters at portals entry in native tissue environments. We illustrate this concept by introducing fluorescent Aspergillus reporter (FLARE) conidia that simultaneously report phagocytic uptake fungal viability during cellular interactions with the murine respiratory innate immune system. Our studies using FLARE reveal stepwise cell-type-specific requirements for CARD9...
Unmasking an agent of inflammatory anemia Infectious and autoimmune diseases are associated with thrombocytopenia. A severe form cytopenia called macrophage activation syndrome (MAS) may occur during rheumatological disorders viral infections. Akilesh et al. show that monocyte recognition self- or pathogen-derived nucleic acids via Toll-like receptors 7 9 (TLR7 TLR9) drives MAS-like disease in mice. TLR7 TLR9 signaling monocytes causes these cells to differentiate into hematophagocytes...
Autoantibodies to nuclear antigens are hallmarks of systemic lupus erythematosus (SLE) where they contribute pathogenesis. However, there remains a gap in our knowledge regarding how different isotypes autoantibodies this autoimmune disease, including the production critical type I interferon (IFN) cytokines by plasmacytoid dendritic cells (pDCs) response immune complexes (ICs). We focused on IgA, which is second-most prevalent isotype serum and, along with IgG, deposited glomeruli...
Abstract Prior studies have revealed that alternative mRNA splicing of the mouse NKG2D gene generates receptors associate with either DAP10 or DAP12 transmembrane adapter signaling proteins. We report function is normal in human patients lacking functional DAP12, indicating sufficient for signal transduction. Further, we show incapable associating and provide evidence structural differences account species-specific difference this immune receptor.
Toll-like receptor (TLR), a ligand for single-stranded RNA, has been implicated in the development of pathogenic anti-RNA autoantibodies both systemic lupus erythematous (SLE) patients and murine models lupus. It is still unclear, however, where how TLR7-mediated interactions affect autoreactive B cells. We found that overexpression TLR7 transgenic mice (TLR7.1Tg) leads to marked alterations transitional (T1) cells, associated with their expansion proliferation within splenic red pulp (RP)....
Toll-like receptors (TLRs) recognize pathogens and their components, thereby initiating immune responses to infectious organisms. TLR ligation leads the activation of NF-κB MAPKs through well-defined pathways, but it has remained unclear how signaling activates PI3K, which provides an inhibitory pathway limiting responses. Here, we show that adapter B-cell adaptor for PI3K (BCAP) links activation. BCAP-deficient macrophages mice are hyperresponsive agonists have reduced The ability BCAP...
Outside-in signals from β(2) integrins require immunoreceptor tyrosine-based activation motif adapters in myeloid cells that are known to dampen TLR responses. However, the relationship between and regulation is unclear. Here we show deficiency (Itgb2(-/-) ) causes hyperresponsiveness stimulation, demonstrating inhibit downstream of ligation. Itgb2(-/-) macrophages dendritic produced more IL-12 IL-6 than WT when stimulated with agonists mice inflammatory cytokines injected LPS....