A5070695623- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- Wound Healing and Treatments
- Dermatology and Skin Diseases
- Monoclonal and Polyclonal Antibodies Research
- Neuropeptides and Animal Physiology
- Hair Growth and Disorders
- Inflammation biomarkers and pathways
- Virus-based gene therapy research
- IL-33, ST2, and ILC Pathways
- Cell Adhesion Molecules Research
- Galectins and Cancer Biology
- Contact Dermatitis and Allergies
- Axon Guidance and Neuronal Signaling
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Immunology Research
- Silk-based biomaterials and applications
- Glaucoma and retinal disorders
- Inflammasome and immune disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Heat shock proteins research
Scripps Research Institute
2014-2023
Universidade Federal do Paraná
2023
University of California, San Diego
2019-2021
Institut de génétique et de biologie moléculaire et cellulaire
1997-2000
Inserm
2000
Centre National de la Recherche Scientifique
2000
The University of Melbourne
1990-1995
Adoptive T cell therapies (ACTs) hold great promise in cancer treatment, but low overall response rates patients with solid tumors underscore remaining challenges realizing the potential of this cellular immunotherapy approach. Promoting CD8+ adaptation to tissue residency represents an underutilized promising strategy improve tumor-infiltrating lymphocyte (TIL) function. Here, we report that deletion HIF negative regulator von Hippel-Lindau (VHL) cells induced HIF-1α/HIF-2α-dependent...
Skin Reaction Lymphocytes in the skin known as γδ T cells provide an important barrier against infection and injury. Unlike classical αβ cells, less is about molecular requirements of cell activation. Two studies demonstrate that junctional adhesion molecule–like protein (JAML) a costimulatory molecule for mouse T. Witherden et al. (p. 1205 ; see Perspective by Shaw Huang ) showed JAML, binding to its ligand Coxsackie adenovirus receptor (CAR), leads proliferation, well cytokine growth...
The epidermis, the outer layer of skin, forms a physical and antimicrobial shield to protect body from environmental threats. Skin injury severely compromises epidermal barrier requires immediate repair. Dendritic T cells (DETC) reside in murine epidermis where they sense skin serve as regulators orchestrators immune responses. Here, we determined that TCR stimulation induces IL-17A production by subset DETC. This IL-17A-producing DETC was distinct IFN-γ producers, despite similar surface...
A system that allows the study, in a gentle fashion, of role MHC molecules naive T cell survival is described. Major histocompatibility complex class II–deficient mice were engineered to express Eα chains only thymic epithelial cells tetracycline (tet)-controllable manner. This resulted tet-responsive display surface E complexes, positive selection CD4+8– thymocytes, and generation CD4+ compartment II–barren periphery. Using this system, we have addressed two unresolved issues: half-life...
Nonhealing wounds are a major complication of diseases such as diabetes and rheumatoid arthritis. For efficient tissue repair, inflammatory cells must infiltrate into the damaged to orchestrate wound closure. Hyaluronan is involved in inflammation associated with repair binds surface leukocytes infiltrating sites. Skin γδ T play specialized roles keratinocyte proliferation during repair. Here, we show that required for hyaluronan deposition extracellular matrix (ECM) subsequent macrophage...
Abstract A unique population of T lymphocytes, designated dendritic epidermal cells (DETC), homes to the murine epidermis during fetal development. DETC express a canonical γδ TCR, Vγ3/Vδ1, which recognizes Ag expressed on damaged, stressed, or transformed keratinocytes. Recently, were shown play key role in complex process wound repair. To examine TCR localization epidermis, maintenance skin, and activation vivo, we analyzed TCRδ−/− mouse. Unlike previous reports skin was found be devoid...
Coxsackie and adenovirus receptor (CAR) is the primary cellular for group B coxsackieviruses most serotypes plays a crucial role in adenoviral gene therapy. Recent discovery of interaction between junctional adhesion molecule-like protein (JAML) CAR uncovered important functional roles immunity, inflammation, tissue homeostasis. Crystal structures JAML ectodomain (2.2 angstroms) its complex with (2.8 reveal an unusual immunoglobulin-domain assembly charged interface that confers high...
TCR-specific activation is pivotal to dendritic epidermal T cell (DETC) function during cutaneous wound repair. However, DETC TCR ligands are uncharacterized, and little known about their expression patterns kinetics. Using soluble tetramers, we demonstrate that not constitutively expressed in healthy tissue but rapidly upregulated following wounding on keratinocytes bordering edges. Ligand tightly regulated, with downmodulation activation. Early inhibition of TCR-ligand interactions using...
Abstract Substances that penetrate the skin surface can act as allergens and induce a T cell–mediated inflammatory disease called contact hypersensitivity (CHS). IL-17 is key cytokine in CHS was originally thought to be produced solely by CD4+ cells. However, it now known several cell types, including γδ cells, produce IL-17. In this study, we determine role of especially dendritic epidermal cells (DETCs), CHS. Using well-established model for which 2,4-dinitrofluorobenzene (DNFB) used...
The cutaneous wound-healing program is a product of complex interplay among diverse cell types within the skin. One fundamental process that mediated by these reciprocal interactions mobilization local stem pools to promote tissue regeneration and repair. Using ablation epidermal caspase-8 as model wound healing in Mus musculus, we analyzed signaling components responsible for epithelial proliferation. We found IL-1α IL-7 secreted from keratinocytes work tandem expand activated population...
Among T cell subsets, gamma delta cells uniquely display an Ag receptor-based tissue distribution, but what defines their preferential homing and homeostasis is unknown. To address this question, we studied the resources that control in secondary lymphoid organs. We found alpha beta are controlled by partially overlapping resources, because acute homeostatic proliferation of was inhibited intact compartment, both populations were dependent on IL-7 IL-15. Significantly, to undergo...
We have examined the role of CD81 in activation murine splenic alphabeta T cells. Expression molecule on cells increases following activation, raising possibility a for this progression process. Using an vitro costimulation assay, we show that can function as costimulatory both CD4+ and CD8+ This functions independently CD28, unlike through is susceptible to inhibition by cyclosporin A. Strikingly, pattern cytokine production elicited via unique. IL-2 was not up-regulated, whereas IFN-gamma...
T cells are critical mediators of antitumor immunity and a major target for cancer immunotherapy. Antibody blockade inhibitory receptors such as PD-1 can partially restore the activity tumor-infiltrating lymphocytes (TILs). However, activation signals required to promote TIL responses less well characterized. Here we show that CD8 γδ is supported by interactions between junctional adhesion molecule–like protein (JAML) on its ligand coxsackie adenovirus receptor (CXADR) within tumor tissue....