• The membrane-anchored form of Spitz, a transforming growth factor (TGF)- α -like molecule that is an epidermal growth factor receptor (EGFR) ligand in Drosophila , is inactive but is activated following proteolytic cleavage to yield a soluble protein [ 11 ]. (hindawi.com)
  • Specific antigen engagement initiates two BCR-mediated processes: the transmission of intracellular signals regulating entry into cell cycle ( 2 , 3 ) and antigen internalization before its processing and presentation in association with MHC to specific T cells ( 4 ). (pnas.org)
  • In this study, we describe a novel function for the mouse RCA type I membrane protein Crry/p65 as a costimulatory molecule in CD4 + T cell activation. (jimmunol.org)
  • This mechanism is effective over a wide range of antigen affinities but depends on exceeding a tightly regulated avidity threshold necessary for BCR-mediated internalization and CD1d-dependent presentation of particulate antigenic lipid. (pnas.org)
  • Thus, we have demonstrated that in response to particulate antigenic lipids iNKT cells are recruited for the assistance of B cell activation, resulting in the enhancement of specific antibody responses. (pnas.org)
  • For many years, peptides were assumed to be the only antigenic determinant for initiating T cell responses. (pnas.org)
  • As CD1d is expressed by B cells, it is conceivable that BCR-mediated internalization could also play a role in CD1d-dependent presentation of antigenic lipids to T cells. (pnas.org)
  • The antigen may be a tumour associated antigen, pathogenic organism antigen, autoimmune antigen, immunogenic fragment thereof, or a nucleic acid coding therefor. (google.com)
  • 5 . A method according to claim 4 wherein the antigen is selected from the group consisting of tumor antigens, autoimmune antigens and an antigen isolated from a pathogenic organism. (google.com)
  • Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. (sciencemag.org)
  • Mast cells (MCs) 3 are the principal effector cells of allergy because of their ability to release a wide range of pharmacologically active mediators upon contact with allergens ( 1 , 2 , 3 ). (jimmunol.org)
  • Jordan, M.S., Singer, A.L. & Koretzky, G.A. Adaptors as central mediators of signal transduction in immune cells. (nature.com)
  • Production of chemical mediators from lamina propria cells was measured by real-time reverse transcription PCR. (bmj.com)
  • EFmDREAM tg mice showed reduced T‐cell proliferation. (embopress.org)
  • The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. (springer.com)
  • When given to diseased mice, the engineered T cells targeted and killed B cells that express antibodies targeting desmoglein 3, hinting that such a strategy may be an effective way to treat antibody-driven autoimmune diseases. (sciencemag.org)
  • A subset of T cells known as invariant natural killer T (iNKT) cells are defined by their expression of a restricted TCR repertoire, consisting of a canonical Vα14-Jα18 or Vα24-Jα18 chain in mice and humans, respectively. (pnas.org)
  • Using mice bearing the Lewis lung carcinoma (3LL), we asked whether one or more of the enzymatic pathways that metabolize l -Arg were present in the tumor microenvironment and could explain the molecular alterations seen in T cells from patients with cancer. (aacrjournals.org)
  • To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. (ahajournals.org)
  • Intracerebroventricular delivery of (pro)renin receptor short-hairpin RNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared with the control virus treatment in double-transgenic mice. (ahajournals.org)
  • Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double-transgenic mice. (ahajournals.org)
  • We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice. (ahajournals.org)
  • We redirected central memory T cells to express second-generation CAR-specific for CS1 and adoptively transferred them into multiple myeloma tumor-bearing mice to test their anti-multiple myeloma activity. (aacrjournals.org)
  • Finally, CS1 CAR T cells and lenalidomide were administered to treat multiple myeloma-bearing mice as combinatorial therapy. (aacrjournals.org)
  • CS1 CAR T cells exhibited efficient antitumor activity when adoptively transferred into mice. (aacrjournals.org)
  • Byth KF, Conroy LA, Howlett S, Smith AJ, May J, Alexander DR, Holmes N (1996) CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B-cell maturation. (springer.com)
  • Design The dextran sodium sulfate (DSS)-induced colitis model was used in wild-type (WT), LMIR3 −/− , mast cell-deficient Kit W-sh/W-sh , Kit W-sh/W-sh LMIR3 −/− or Kit W-sh/W-sh mice engrafted with WT or LMIR3 −/− bone marrow-derived mast cells (BMMCs). (bmj.com)
  • Kit W-sh/W-sh mice harbouring LMIR3 −/− mast cells exhibited more severe colitis than those harbouring WT mast cells. (bmj.com)
  • Conclusions LMIR3-deficient colonic mast cells were pivotal in the exacerbation of DSS-induced colitis in LMIR3 −/− mice. (bmj.com)
  • The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. (ahajournals.org)
  • Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor, and vasopressin mRNA levels. (ahajournals.org)
  • These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease in sympathetic tone and an improvement of the baroreflex sensitivity. (ahajournals.org)
  • In addition, brain-targeted (pro)renin receptor knockdown is associated with downregulation of angiotensin II type 1 receptor and vasopressin levels. (ahajournals.org)
  • Theoretically, complete suppression of RAAS by renin inhibition has broad applicability in disease states associated with excess activation of the RAAS and continued production of angiotensin II (Ang II) despite angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy. (ahajournals.org)
  • Acuto, O. & Cantrell, D. T cell activation and the cytoskeleton. (nature.com)
  • This strategy thereby avoids the requirement of antigen processing and presentation by the target cell and is applicable to non-classical T cell targets like carbohydrates ( 3 ). (frontiersin.org)
  • Tumor-associated myeloid cells also expressed high levels of cationic amino acid transporter 2B, which allowed them to rapidly incorporate l -Arginine ( l -Arg) and deplete extracellular l -Arg in vitro . (aacrjournals.org)
  • Objective Extracellular ATP mediates mast cell-dependent intestinal inflammation via P2X7 purinoceptors. (bmj.com)
  • Extracellular ATP mediates mast cell-dependent intestinal inflammation via P2X7 purinoceptors. (bmj.com)
  • A major barrier to developing therapeutics to prevent CAR T cell-mediated neurotoxicity is the lack of clinically relevant models. (aacrjournals.org)
  • Chang CC, Campoli M, Ferrone S. Classical and nonclassical HLA class I antigen and NK Cell-activating ligand changes in malignant cells: current challenges and future directions. (springer.com)
  • Brummer T, Shaw PE, Reth M, Misawa Y (2002) Inducible gene deletion reveals different roles for B-Raf and Raf-1 in B-cell antigen receptor signalling. (springer.com)
  • When allergen-harboring mast cells were stimulated, the intracellular allergens were expelled intact and shown to activate adjacent mast cells. (jimmunol.org)
  • On the one hand, for several alloreactive T cell clones the exact peptides recognized, which can be present at both high and low copy numbers, have been identified ( 9 )( 10 )( 11 )( 12 )( 13 ). (rupress.org)
  • Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. (springer.com)
  • In contrast patched raft components and patches of transferrin receptor as a non-raft marker were sharply separated. (rupress.org)
  • Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells. (springer.com)
  • In several human malignancies, the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival. (hindawi.com)
  • In addition, expression of the CD28 ligands B7-1 and B7-2 in murine splenic B cells is increased by CR2/CR1/surface Ig co-cross-linking ( 9 ). (jimmunol.org)
  • CAR expression on the surfaces of the T cells was detected by flow cytometry andWestern blot. (springer.com)
  • Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. (frontiersin.org)
  • Using a 3LL murine lung carcinoma model we tested whether arginase I was produced in the tumor microenvironment and could decrease CD3ζ expression and impair T-cell function. (aacrjournals.org)
  • l -Arg depletion by tumor-associated myeloid cells blocked the re-expression of CD3ζ in stimulated T cells and inhibited antigen-specific proliferation of OT-1 and OT-2 cells. (aacrjournals.org)
  • 6 , 7 Transgenic rats with human PRR expression targeted to vascular smooth muscle cells exhibit hypertension and increased plasma aldosterone, suggesting a pathological role of the PRR in raising blood pressure (BP). (ahajournals.org)
  • SAPK/JNK activation was completely abolished in the absence of MKK7, even though expression of MKK4 was strongly upregulated in mkk7 − / − mast cell lines, and phosphorylation of MKK4 occurred normally in response to multiple stress stimuli. (pubmedcentralcanada.ca)
  • 2 Recent studies show that renin and its precursor prorenin can bind the (pro)renin receptor (PRR), suggesting a more complex contribution of renin and prorenin via PRR. (ahajournals.org)
  • The nonreceptor tyrosine kinases Janus kinase (Jak)1 and Jak3, constitutively associated with IL-4Rα and γc, respectively ( 6 )( 7 )( 8 ), become activated after IL-4 binding to its receptor and phosphorylate some or all of the conserved tyrosines of IL-4Rα. (rupress.org)
  • Finkelstein, L.D. & Schwartzberg, P.L. Tec kinases: shaping T-cell activation through actin. (nature.com)
  • Duox1 bound to inositol 1,4,5-trisphosphate receptor 1 and was required for early T cell receptor (TCR)-stimulated production of hydrogen peroxide (H 2 O 2 ) through a pathway that was dependent on TCR-proximal kinases. (sciencemag.org)
  • EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro . (springer.com)
  • Furthermore, lenalidomide enhanced the antitumor activity and persistence of adoptively transferred CS1 CAR T cells in vivo . (aacrjournals.org)
  • Autoimmune diseases such as lupus and rheumatoid arthritis lack therapies that specifically target only the disease-causing cells. (sciencemag.org)
  • CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease. (sciencemag.org)
  • iNKT cells are activated in response to a variety of infections and during inflammatory and autoimmune diseases ( 12 , 13 ). (pnas.org)
  • Another surprise is that such diverse receptors in an individual do not react with any structures contained in the self body (self-antigens) in principle, which is called self-tolerance. (springer.com)
  • Therefore, arginase I production by mature myeloid cells in the tumor microenvironment may be a central mechanism for tumor evasion and may represent a target for new therapies. (aacrjournals.org)
  • Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. (springer.com)
  • Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. (frontiersin.org)