A5074513395- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Dermatology and Skin Diseases
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- Autoimmune Bullous Skin Diseases
- Cytomegalovirus and herpesvirus research
- Autoimmune and Inflammatory Disorders
- Cutaneous Melanoma Detection and Management
- Lymphatic System and Diseases
- Dermatological and COVID-19 studies
- Salmonella and Campylobacter epidemiology
- Cancer Cells and Metastasis
- IgG4-Related and Inflammatory Diseases
- Sympathectomy and Hyperhidrosis Treatments
- Viral gastroenteritis research and epidemiology
- Cellular Mechanics and Interactions
- Electrohydrodynamics and Fluid Dynamics
- Tryptophan and brain disorders
- 3D Printing in Biomedical Research
- Sphingolipid Metabolism and Signaling
Thomas Jefferson University
2017-2024
Sidney Kimmel Cancer Center
2019-2024
University of Pennsylvania
2009-2017
University of Delaware
2012
Stanford University
2003-2007
VA Palo Alto Health Care System
2003-2007
Charité - Universitätsmedizin Berlin
2002-2006
German Rheumatism Research Centre
2002-2004
Humboldt-Universität zu Berlin
2002-2004
Regulatory T cells (Tregs) fulfill a central role in immune regulation. We reported previously that the integrin αEβ7 discriminates distinct subsets of murine CD4+ regulatory cells. Use this marker has now helped to unravel fundamental dichotomy among αE−CD25+ expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues. In contrast, αE-positive (CD25+ CD25−) displayed an effector/memory phenotype expressing high levels E/P-selectin–binding ligands, multiple adhesion...
Abstract Plasma blasts formed during memory immune responses emigrate from the spleen to migrate into bone marrow and chronically inflamed tissues where they differentiate long-lived plasma cells. In this study, we analyze chemokine responsiveness of after secondary immunization with OVA. Starting day 4 within ∼48 h, OVA-specific appear in marrow. Although these migratory cells have lost their many B cell attracting chemokines, e.g., CXC ligand (CXCL)13 (B lymphocyte chemoattractant), toward...
B cells infiltrate the skin in many chronic inflammatory diseases caused by autoimmunity or infection. Despite potential contribution to disease, skin-associated remain poorly characterized. Using an ovine model of granulomatous inflammation, we demonstrate that increase and skin-draining afferent lymph during inflammation. Surprisingly, are a heterogeneous population is distinct from node cells, with more large lymphocytes as well B-1-like coexpress high levels IgM CD11b. Skin have...
Infection with influenza virus can result in massive pulmonary infiltration and potentially fatal immunopathology. Understanding the endogenous mechanisms that control immunopathology could provide a key to novel adjunct therapies for this disease. Here we show cytokine IL-27 plays crucial role protection from exaggerated inflammation during infection. Using Il-27ra−/− mice, was found limit immunopathology, neutrophil accumulation, dampened TH1 or TH17 responses via IL-10–dependent...
Memory/effector T cells traffic efficiently through extralymphoid tissues, entering from the blood and leaving via afferent lymph. During inflammation, cell into affected tissue dramatically increases; however, dynamics mechanisms of exit inflamed tissues are poorly characterized. In this study, we show, using both a mouse sheep model, that large numbers lymphocytes leave chronically skin. Many capable producing IFN-γ IL-17 also entered draining lymph, demonstrating memory/effector egress...
Abstract The skin is an important barrier organ and frequent target of autoimmunity allergy. In this study, we found innate-like B cells that expressed the anti-inflammatory cytokine IL-10 in humans mice. Unexpectedly, B1 conventional B2 showed differential homing capacities with peritoneal preferentially migrating into inflamed Importantly, skin-homing included IL-10–secreting cells. cell was independent typical trafficking receptors instead required α4β1-integrin. Moreover, constitutively...
Effector T cell migration into inflamed sites greatly exacerbates tissue destruction and disease severity in inflammatory diseases, including graft-versus-host (GVHD). such depends heavily on regulated adhesion migration, but the signaling pathways that coordinate these functions downstream of chemokine receptors are largely unknown. Using conditional knockout mice, we found cells lacking adaptor proteins CRK CRK-like (CRKL) exhibit reduced integrin-dependent adhesion, chemotaxis,...
Abstract Chemokines and their receptors fulfill specialized roles in inflammation under homeostatic conditions. CCR7 its ligands, CCL19 CCL21, are involved lymphocyte recirculation through secondary lymphoid organs additionally navigate lymphocytes into distinct tissue compartments. The role of the migration polarized T effector/memory cell subsets vivo is still poorly understood. We therefore analyzed murine human CD4+ cytokine-producing cells developed for chemotactic reactivity to...
Memory/effector T cells efficiently migrate into extralymphoid tissues and sites of infection, providing immunosurveillance a first line defense against invading pathogens. Even though it is potential means to regulate the size, quality, duration tissue infiltrate, cell egress from infected poorly understood. Using mouse model influenza A virus we found that CD8 effector egressed lung in CCR7-dependent manner. In contrast, following antigen recognition, decreased CCR7 function was reduced...
The lung is an important entry site for respiratory pathogens such as influenza A virus. In order to combat invading infectious agents, effector/memory T cells home the and other peripheral tissues well lymphoid organs. this process, chemokines their receptors fulfill roles in guidance of into organs specialized microenvironments within tissues. study, we determined if CD4(+) residing different compartments draining lymph nodes virus-infected naïve mice express allowing recirculation...
Abstract Memory/effector T cells recirculate through extralymphoid tissues by entering from blood and egressing via afferent lymph. Although cell entry into effector sites is key to inflammation, the relevance of egress this process unknown. In study, we found that Ag recognition at site reduced tissue proinflammatory Th1 in a mouse model delayed hypersensitivity. Transgenic expression “tissue exit receptor” CCR7 enhanced lymphatic Ag-sequestered inflamed alleviated inflammation. contrast,...
Background Migration of antigen-experienced T cells to secondary lymphoid organs and the site antigenic-challenge is a mandatory prerequisite for precise functioning adaptive immune responses. The surface molecule CD152 (CTLA-4) mostly considered as negative regulator cell activation during It currently unknown whether can also influence chemokine-driven migration. Methodology/Principal Findings We analyzed consequences signaling on Th migration using chemotaxis assays in vitro radioactive...
IL-10+ B cells are critical for immune homeostasis and restraining responses in infection, cancer, inflammation; however, the signals that govern cell differentiation ill-defined. Here we find expand mice lacking secreted IgM ((s)IgM-/-) up to 10-fold relative wildtype (WT) among all major regulatory subsets. The increase is polyclonal presents within 24 hours of birth. In WT mice, sIgM produced prenatally limits expansion cells. Lack high affinity receptor sIgM, FcμR, translates into an...
Abstract Th1- and Th2-polarized immune responses are crucial in the defense against pathogens but can also promote autoimmunity allergy. The chemokine receptors CXCR3 CCR4 have been implicated differential trafficking of IFN-γ- IL-4-producing T cells, respectively, tissue inflammation-specific homing independent cytokine responses. Here, we tested whether CD4+ cells isolated from murine tissues under homeostatic or inflammatory conditions exhibit restricted patterns chemotactic that...
T cell recirculation through extralymphoid tissues is essential to immune surveillance, host defense and inflammation. In this process, cells enter the tissue from blood subsequently leave via afferent lymph. absence of inflammation, require CCR7 expression egress skin or lung, which consistent with constitutive ligand CCL21 on lymphatic endothelium. However, during chronic inflammation alternative chemoattractants come into play, allowing Ccr7-deficient (Ccr7−/−) efficiently affected skin....
Endothelial selectins are crucial for the recruitment of leukocytes into sites inflammation. On T cells, ligands become induced upon differentiation effector/memory stage. Initial in vitro studies suggested a correlation between Th1 phenotype and ligand expression, but whether this also holds true vivo remained uncertain. We here analyzed selectin on CD4+ cells producing IFN-gamma, IL-4 or IL-10, prototypic cytokines Th1, Th2 Tr1 subset, respectively. mice infected with influenza virus,...