A5032348618- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Transplantation: Methods and Outcomes
- Signaling Pathways in Disease
- Omental and Epiploic Conditions
- NF-κB Signaling Pathways
- Galectins and Cancer Biology
- Cytokine Signaling Pathways and Interactions
- Synthesis and Biological Evaluation
- Immunodeficiency and Autoimmune Disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Vitamin D Research Studies
- IL-33, ST2, and ILC Pathways
- Cancer Immunotherapy and Biomarkers
- Drug-Induced Adverse Reactions
- Chronic Lymphocytic Leukemia Research
- Neuroscience and Neuropharmacology Research
- Lymphatic System and Diseases
- Macrophage Migration Inhibitory Factor
- Nerve injury and regeneration
Loyola University Chicago
2013-2023
May Institute
2022
Loyola University Medical Center
2011-2018
Augusta University
1999-2009
Bipar
2009
Institute for Advanced Medical Research
2004
Japan Science and Technology Agency
1997-2004
Chiba University
2002-2004
The University of Tokyo
2004
Tokyo University of Science
2004
The T cell antigen receptor (TCR) initiates signals by interacting with cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif [called the recognition activation (ARAM)] that is contained in TCRζ and CD3 chains. TCR stimulation induces phosphorylation of several cellular substrates, including ARAMs. Lck kinase activity required for two conserved residues an ARAM. This leads to recruitment second PTK, ZAP-70, both ZAP-70 Src homology 2 domains its phosphorylation....
Protein tyrosine kinases (PTKs) play an integral role in T cell activation and differentiation. Defects the Src-family PTKs mice lines have resulted variable defects thymic development antigen receptor (TCR) signal transduction. Here, three siblings are described with autosomal recessive form of severe combined immunodeficiency disease (SCID) which ZAP-70, a non-Src PTK, is absent as result mutations ZAP-70 gene. This absence associated TCR transduction, suggesting important functional for ZAP-70.
Abstract In mice, immunoregulatory APCs express the dendritic cell (DC) marker CD11c, and one or more distinctive markers (CD8α, B220, DX5). this study, we show that expression of tryptophan-degrading enzyme indoleamine 2,3 dioxygenase (IDO) is selectively induced in specific splenic DC subsets when mice were exposed to synthetic immunomodulatory reagent CTLA4-Ig. CTLA4-Ig did not induce IDO macrophages lymphoid cells. Induction completely blocked clonal expansion T cells from TCR transgenic...
Abstract Sialic acid‐binding immunoglobulin‐type lectins (Siglecs) are a family of that mediate protein‐carbohydrate interactions via sialic acids attached to glycoproteins or glycolipids. Most the CD33‐related Siglecs (CD33rSiglecs), major subfamily rapidly evolving Siglecs, contain cytoplasmic signaling domain consisting immunoreceptor tyrosine‐based inhibitory motif (ITIM) and switch (ITSM) suppressive signals for lymphoid myeloid cells. While most CD33rSiglecs expressed by innate immune...
The omentum is a sheet-like tissue attached to the greater curvature of stomach and contains secondary lymphoid organs called milky spots. has been used for its healing potential over 100 years by transposing omental pedicle injured (omental transposition), but mechanism which helps process damaged tissues not well understood. Omental transposition promotes expansion pancreatic islets, hepatocytes, embryonic kidney, neurons. cells (OCs) can be activated foreign bodies in vivo. Once...
The activation of downstream signaling pathways both T cell receptor (TCR) and interleukin 4 (IL-4R) is essential for helper type 2 (Th2) development, which central to understanding immune responses against helminthic parasites in allergic autoimmune diseases. However, little known about how these two distinct cooperate with each other induce Th2 cells. Here, we show that successful development depends on the effectiveness TCR-induced calcineurin. An inhibitor calcineurin activation, FK506,...
The Src family protein-tyrosine kinase, Fyn, is associated with the T cell receptor (TCR) and plays an important role in TCR-mediated signaling. We found that a human leukemia virus type 1-infected line, Hayai, overexpressed Fyn. To identify molecules downstream of we analyzed tyrosine phosphorylation cellular proteins cells. In 68-kDa protein was constitutively tyrosine-phosphorylated. coimmunoprecipitated various signaling such as phospholipase C γ1, phosphatidylinositol 3-kinase p85...
A functional cDNA cloning system was developed by using a retrovirus library encoding CD8-chimeric proteins and nuclear factor of activated T cells (NFAT)-GFP reporter cell line to identify molecules inducing NFAT activation. By this strategy, activating molecule 1 (NFAM1) cloned as an immunoreceptor tyrosine-based activation motif (ITAM)-bearing surface belonging the Ig superfamily is predominantly expressed in spleen B cells. NFAM1 crosslinking induced ITAM phosphorylation, ZAP-70/Syk...
Engagement of the T cell antigen receptor (TCR) rapidly induces multiple signal transduction pathways, including ERK activation. Here, we report a critical role for at late stage Inhibition pathway 2–6 h after start TCR stimulation significantly impaired interleukin-2 (IL-2) production, whereas same treatment during first 2 had no effect. inhibition nuclear translocation c-Rel with minimum reduction NF-AT activity. Requirement sustained activation was also confirmed using primary cells. To...
T cell activation by the specific Ag results in dramatic changes of phenotype that include a rapid and profound down-regulation degradation triggered TCRs. In this work, we investigated fate TCR-associated ZAP-70 kinase Ag-stimulated cells. cells stimulated peptide-pulsed APCs undergo an dose-dependent decrease total cellular content ZAP-70, as detected FACS analysis confocal microscopy on fixed permeabilized cell-APC conjugates Western blot lysates. The time course consumption overlaps with...
A variable region (V delta 5) of the T-cell receptor (TcR) chain that is preferentially expressed in adult murine thymocytes located 2.5 kilobases 3' constant (C delta) element. The V 5 coding sequence a transcriptional orientation opposite J (joining region) and C elements rearranges by inversion. divided into four exons, three which encode amino acids TcR polypeptide, fourth comprises entire untranslated region. In this respect, resembles alpha rather than beta or gamma.
Abstract Naturally arising CD4+CD25+FoxP3+ regulatory T cells (nTregs) have an essential role in maintenance of immune homeostasis and peripheral tolerance. Previously, we reported that conventional CD4+ CD8+ undergo p53-induced CD28-dependent apoptosis (PICA) when stimulated with a combination immobilized anti-CD3 anti-CD28 Abs, whereas nTregs expand robustly under the same conditions, suggesting there is differential survival mechanism against PICA between nTregs. In this study,...
Antigenic stimulation of the T-cell antigen receptor initiates signal transduction through immunoreceptor tyrosine-based activation motifs (ITAMs). When its two tyrosines are phosphorylated, ITAM forms a binding site for ZAP-70, one cytoplasmic protein tyrosine kinases essential activation. The signaling process that follows ZAP-70 to has been analyzed by construction fusion proteins localize plasma membrane. We found membrane-localized induce late events such as nuclear factor activated T...
The immunoregulatory functions of vitamin D have been well documented in various immunological disorders, including multiple sclerosis, arthritis, and asthma. IL-10 is considered a chief effector molecule that promotes the D-induced immunosuppressive states T cells accessory cells. In this article, we demonstrate active form D, 1,25-dihydroxyvitamin D3 (calcitriol), has profound inhibitory effect on development human Th9, CD4 cell subset highly associated with asthma, an IL-10-independent...
Shc, a prototypic adapter molecule, has been implicated in T cell receptor (TCR) signal transduction, but its role not identified clearly. Here we report that Shc is essential for TCR-induced IL-2 production dispensable CD69 or CD25 expression. Engagement of TCR mutant Jurkat cells lacking fails to produce because impaired mitogen-activated protein kinase activation. Activation c-Rel, transcription factor expression, was also. In contrast, activation nuclear activated and expression...
Ag receptor stimulation of preactivated T cells causes rapid cell death in an IL-2- and Fas-dependent manner. This phenomenon, known as activation-induced (AICD), plays a pivotal role the removal Ag-reactive after initial expansion. In this study, we report novel form apoptosis that is distinct from classic AICD. When peripheral were activated with anti-CD3 anti-CD28 Abs precoated onto plastic plates, CD4(+)CD25(-) CD8 initially expanded but underwent massive 4 d. Unlike AICD, type pathway...
Abstract A major obstacle hindering the development of effective immunity against viral infections, their associated disease, and certain cancers is inherent genomic instability. Accumulation mutations can alter processing presentation antigens recognized by antibodies T cells that lead to immune escape variants. Use an agent intrinsically combat rapidly mutating or cancer-associated would be quite advantageous in developing such disease. We propose harboring cross-reactive TCRs could serve...