Contact hypersensitivity (CHS) is a T cell response to hapten skin challenge of sensitized individuals proposed be mediated by hapten-primed CD8 cytolytic cells. Effector recruitment into sites elicit CHS requires prior CXCL1- and CXCL2-mediated neutrophil infiltration the site. We investigated whether activities directing in 2,4-dinitro-1-fluorobenzene (DNFB) required Fas ligand (FasL) perforin expression. Although DNFB sensitization gld/perforin-/- mice induced hapten-specific cells...

Abstract The ezrin-radixin-moesin proteins regulate B lymphocyte activation via their effect on BCR diffusion and microclustering. This relies ability to dynamically tether the plasma membrane with actin filaments that is in turn facilitated by phosphorylation of conserved threonine residue actin-binding domain. In this study, we describe a novel function ezrin regulating JNK mediated tyrosine (Y353) unconserved moesin radixin. BCR, but not CD40, TLR4, or CXCR5 stimulation, induced at Y353...

B cell chemotaxis occurs in response to specific chemokine gradients and is critical for homeostasis immune response. The molecular regulation of membrane-actin interactions during migration poorly understood. In this study, we report a role ezrin, member the membrane-cytoskeleton cross-linking ezrin-radixin-moesin proteins, earliest steps polarization chemotaxis. We visualized chemokine-induced changes murine morphology using scanning electron microscopy spatiotemporal dynamics ezrin cells...

Inflammasome signaling is kept in check by the kinase Lyn.

Follicular regulatory T cells (Tfr) can play opposite roles in the regulation of germinal center (GC) responses. Depending on studies, Tfr suppress or support GC and B cell affinity maturation. However, which factors determine positive vs. negative effects is unclear. In this study, we show that centrocytes express MYC up-regulate expression CCL3 chemokine needed for both by Tfr. cell–intrinsic contributes to Tfr-dependent selection foreign Ag–specific cells. At same time, critical direct...

Abstract Ezrin is a member of the ezrin–radixin–moesin family membrane-actin cytoskeleton cross-linkers that participate in variety cellular processes. In B cells, phosphorylation ezrin at different sites regulates multiple processes, such as lipid raft coalescence, BCR diffusion, microclustering, and endosomal JNK activation. this study, we generated mice with conditional deletion cell lineage to investigate physiological significance ezrin’s function Ag receptor–mediated activation humoral...

Intestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease poorly understood, although it established circulating pathogenic natural IgM, which primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as marker T later found be present on some subsets B in humans; however, whether plays any role intestinal...

Abstract IL-10 produced by B cells is important for controlling inflammation, thus underscoring the need to identify mechanisms regulating its production. In this study, we demonstrate that conditional deletion of ezrin in increases production induced TLR4 ligation. The MyD88-independent Toll/IL-1R domain–containing adapter inducing IFN-β–IFN regulatory factor 3 pathway required Ezrin-deficient produce higher upon LPS stimulation. Treatment with a novel small-molecule inhibitor induces...

The molecular regulation of recruitment and assembly signalosomes near the B cell receptor (BCR) is poorly understood. We have previously demonstrated a role for ERM family protein ezrin in regulating antigen-dependent lipid raft coalescence cells. In this study, we addressed possibility that may collaborate with other adaptor proteins to regulate signalosome dynamics at membrane. Using mass spectrometry-based proteomics analysis, identified Myo18aα as novel binding partner ezrin. an...

Abstract Introduction: The efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL) is limited by acute toxic events, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS). Identification biomarkers toxicities can allow for selection high-risk elucidate targetable mechanisms mitigation. Previous biomarker studies have been constrained relatively narrow panels...

Abstract Genetic deletion of the Src family tyrosine kinase Lyn in mice recapitulates human systemic lupus erythematosus, characterized by hyperactive BCR signaling, splenomegaly, autoantibody generation, and glomerulonephritis. However, molecular regulators autoimmunity Lyn-deficient remain poorly characterized. In this study, we report that conditional membrane–cytoskeleton linker protein ezrin B cells (double knockout [DKO] mice) ameliorates cell activation pathogenesis. from DKO respond...

Intermediate and high-risk rhabdomyosarcoma (RMS) patients have poor prognosis with available treatment options, highlighting a clear unmet need for identification of novel therapeutic strategies. Ezrin-radixin-moesin (ERM) family members are membrane-cytoskeleton linker proteins well-defined roles in tumor metastasis, growth, survival. ERM protein activity is regulated by dynamic changes the phosphorylation at conserved threonine residue their C-terminal actin-binding domain. Interestingly,...

We investigated the function of newly discovered myosin family protein 18A (Myo18A) in Ab-mediated immunity by generating B cell-conditional Myo18A-deficient mice. Myo18A deficiency led to expansion bone marrow progenitor cells and mature secondary lymphoid organs. mice displayed serum IgM hyperglobulinemia increased splenic IgM-secreting cells, with older switching IgG1 autoantibody development. Immunization inactivated influenza virus development more potent neutralizing Abs against major...

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma. However, widespread use deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), that induce morbidity require close monitoring. Identification host biochemical signatures predict severity time-to-onset CRS...

Nutritional problem of adolescent girls are common throughout the country. They encounter a series serious nutritional challenges not only affecting their growth and development but also livelihood as adults. Furthermore status has important implication in terms physical work capacity adverse reproductive outcome. Therefore, present investigation was undertaken to study supplementation impact iron folic acid capsule with without thandaion anemic girls. Thandaiwas prepared by grinding...

Abstract Generation of high affinity, broadly neutralizing antibodies has remained a holy grail in influenza and malaria. Appropriate B cell responses are essential for producing to combat these infections. Additionally, cytokines their receptors known orchestrate the immune response infections on several levels. However, regulation antibody production by cytokine cells is not well understood. The anti-inflammatory cytokine, IL-10 activates JAK-STAT pathway upon binding receptor (IL-10R),...

Abstract B cell chemotaxis occurs in response to specific chemokine gradients and is critical for homeostasis immune response. The molecular regulation of membrane-actin interactions during migration poorly understood. In this study we report a role ezrin, member the membrane-cytoskeleton crosslinking Ezrin-Radixin-Moesin (ERM) proteins, earliest steps polarization chemotaxis. We visualized chemokine-induced changes murine morphology using scanning electron microscopy, spatiotemporal...

Purpose: The efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) patients is limited by acute toxicities, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS). Previous biomarker studies have been constrained narrow protein panels time points. We employed NULISATM, a novel ultrasensitive assay capable simultaneously quantifying 204 proteins, to identify temporal proteome associations with...

Abstract Sex bias is well documented in autoimmune diseases, cancer and immune responses to infectious agents. Here, we investigated if pre-treatment risk factors that influence the survival of B-cell non-Hodgkin lymphoma (NHL) patients after anti-CD19 CAR T-cell therapy are sexually dimorphic. We measured pre-leukapheresis tumor burden (lactate dehydrogenase levels), C-reactive protein (CRP) serum cytokine chemokine concentration 67 NHL treated with axicabtagene ciloleucel (axi-cel) or...