- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Biosimilars and Bioanalytical Methods
- Peptidase Inhibition and Analysis
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- HIV/AIDS drug development and treatment
- Viral Infections and Outbreaks Research
- Axon Guidance and Neuronal Signaling
- Viral Infections and Vectors
- Cancer Cells and Metastasis
- Microscopic Colitis
- Reproductive System and Pregnancy
Robert Koch Institute
2016-2017
Biogen (United States)
2002-2014
Clarion University
2013
Biogen (Switzerland)
2004-2008
Maastricht University
2005
Incyte (United States)
2005
Alnylam Pharmaceuticals (United States)
2005
Garvan Institute of Medical Research
2003-2005
International Vaccine Institute
2004-2005
Seoul National University
2005
M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be principal sites for sampling gut luminal antigens. Thus, PP have long been considered gatekeepers mucosal immune system. Here, we report a distinct gateway uptake bacteria: clusters non-follicle-associated epithelium-associated Ulex europaeus agglutinin (UEA)-1 + cells, which designated intestinal villous cells. Interestingly, developed various [or gut-associated lymphoid tissue (GALT)]-null mice,...
For more than a decade, the biological roles and apparent redundancy of cytokines tumor necrosis factor (TNF) lymphotoxin (LT) have been debated. LT alpha exists in its soluble form as homotrimer, which like TNF only binds receptors, TNF-R55 or TNF-R75. The cell surface heteromer beta subunits this complex specifically receptor (LT beta-R). To discriminate functions systems, beta-R-immunoglobulin (Ig) TNF-R-Ig fusion proteins were introduced into embryonic circulation by injecting pregnant...
The glycoproteins (GP) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. Despite extensive study, a receptor for deadly filoviruses Ebolavirus and Marburgvirus has yet to be identified characterized. Here, we show that T-cell Ig mucin domain 1 (TIM-1) binds binding Zaire Ebola virus (EBOV) glycoprotein, ectopic TIM-1 expression in poorly permissive cells enhances EBOV infection 10- 30-fold. Conversely, reduction cell-surface RNAi...
B cell activating factor of the tumor necrosis (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) are closely related ligands within TNF superfamily that play important roles in lymphocyte biology. Both share two receptors—transmembrane activator calcium signal–modulating cyclophilin interactor (TACI) maturation antigen (BCMA)—that predominantly expressed on cells. In addition, BAFF specifically binds receptor, whereas nature postulated APRIL-specific receptor remains elusive....
The cell surface receptor T immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues the TIM-1 IgV are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on viral envelope. liposomes but not phosphatidylcholine competed EBOV pseudovirion and transduction. Further, annexin V (AnxV) substituted domain, supporting a PtdSer-dependent mechanism. Our findings...
The regulation of T cell-mediated immune responses requires a balance between amplification and generation effector function subsequent selective termination by clonal deletion. Although apoptosis previously activated cells can be induced signaling the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell deletion in an antigen-specific fashion. We demonstrate that cross-linking inducible surface molecule CTLA4 mediate human lymphocytes. This appears...
Proper lymph node (LN) development requires tumor necrosis factor-related activation-induced cytokine (TRANCE) expression. Here we demonstrate that the defective LN in TRANCE(-/)- mice correlates with a significant reduction lymphotoxin (LT)alphabeta(+)alpha(4)beta(7)(+)CD45(+)CD4(+)CD3(-) cells and their failure to form clusters rudimentary mesenteric LNs. Transgenic TRANCE overexpression results selective restoration of this cell population into clusters, full development. TRANCE-mediated...
A proliferation-inducing ligand (APRIL) is a of the tumor necrosis factor (TNF) family that stimulates cell growth in vitro and vivo. Expression APRIL highly upregulated many tumors including colon prostate carcinomas. Here we identify B maturation antigen (BCMA) transmembrane activator calcium modulator cyclophilin (CAML) interactor (TACI), two predicted members TNF receptor family, as receptors for APRIL. binds BCMA with higher affinity than TACI. soluble form BCMA, which inhibits...
Mice deficient in lymphotoxin β receptor (LTβR) or interleukin 7 α (IL-7Rα) lack Peyer's patches (PPs). Deficiency CXC chemokine 5 (CXCR5) also severely affects the development of PPs. A molecular network involving these three signaling pathways has been implicated PP organogenesis, but it remains unclear how they are connected during this process. We have shown that organogenesis is initiated at sites containing IL-7Rα+ lymphoid cells and vascular cell adhesion molecule...
Adhesive interactions play an important role in inflammation by promoting leukocyte attachment and extravasation from the vasculature into peripheral tissues. However, importance of adhesion molecules within extracellular matrix–rich environment tissues, which cells must migrate be activated, has not been well explored. We investigated major collagen-binding integrins, α1β1 α2β1, several vivo models inflammation. mAb’s against murine α1 α2 were found to significantly inhibit effector phase...
Both nuclear factor (NF)-kappaB-inducing kinase (NIK) and inhibitor of kappaB (IkappaB) (IKK) have been implicated as essential components for NF-kappaB activation in response to many external stimuli. However, the exact roles NIK IKKalpha cytokine signaling still remain controversial. With use vivo mouse models, rather than with enforced gene-expression systems, we investigated role through type I tumor necrosis (TNF) receptor (TNFR-I) lymphotoxin beta (LTbetaR), a lymphoid organogenesis....
TRAF5 [tumor necrosis factor (TNF) receptor-associated 5] is implicated in NF-κB and c-Jun NH 2 -terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, lymphotoxin-β receptor. To investigate functional role vivo , we generated TRAF5-deficient mice gene targeting. Activation either or tumor factor, CD40 was not abrogated traf5 −/− mice. However, B cells showed defects proliferation up-regulation various surface...
We have previously demonstrated the loss of oral tolerance (OT) in lymphotoxinα − / (LTα −) and TNFα deficient (TNFα LTα mice which defective Peyer's patches (PP) lymph node (LN) development. now studied OT BALB c with differential defects gut-associated lymphoid tissue (GALT) caused by inhibition LTβR signaling during fetal Treatment pregnant LTβR-IgG (LTβRIgG) TNFR I(55)-IgG (TNFR55IgG) abrogates formation PP or mesenteric LN (MLN) (LTβRIgG TNFRIgG) without genetically deleting respective...
To investigate the potential involvement of T helper (Th)2-type responses in murine models intestinal inflammation, we used trinitrobenzene sulfonic acid (TNBS)–hapten to induce inflammatory bowel disease situations where Th1-type with interferon (IFN)-γ synthesis are either diminished or do not occur. Intracolonic administration TNBS normal (IFN-γ+/+) Th1-deficient IFN-γ knockout (IFN-γ−/−) BALB/c mice resulted significant colitis. In IFN-γ−/− mice, crypt inflammation was more severe than...
The lymphotoxin-alpha beta complex (LT alpha beta) is found on the surface of activated lymphocytes and binds to a specific receptor called LT R). In mouse, signaling through this pathway important for lymph node development splenic organization, yet biochemical properties murine are essentially unknown. Here we have used soluble receptor-Ig forms R TNF-R55 mAbs alpha, beta, characterize appearance complexes several common cell lines. Cells that bound also anti-LT in FACS analysis. ability...
To clarify the role of Peyer's patches in oral tolerance induction, BALB/c mice were treated utero with lymphotoxin β-receptor Ig fusion protein to generate lacking patches. When these patch-null fed 25 mg ovalbumin (OVA) before systemic immunization, OVA-specific IgG Ab responses serum and spleen seen, marked contrast low OVA-fed normal mice. Further, high T-cell-proliferative- delayed-type hypersensitivity seen given OVA challenge. Higher levels CD4 + T-cell-derived IFN-γ, IL-4, IL-5,...