A5102934317- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- Autophagy in Disease and Therapy
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Immune cells in cancer
- Prenatal Screening and Diagnostics
- Psoriasis: Treatment and Pathogenesis
- Mesenchymal stem cell research
- Diabetes and associated disorders
- Phagocytosis and Immune Regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Renal and related cancers
- Acute Myeloid Leukemia Research
- IL-33, ST2, and ILC Pathways
- Immune responses and vaccinations
- Reproductive Biology and Fertility
- Extracellular vesicles in disease
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Axon Guidance and Neuronal Signaling
- Chemokine receptors and signaling
- Pancreatic function and diabetes
- Polyomavirus and related diseases
- Erythrocyte Function and Pathophysiology
QIMR Berghofer Medical Research Institute
2012-2024
The University of Queensland
2011-2024
Brisbane School of Theology
2014
Institut Génétique Nantes Atlantique
2009
Inserm
2008-2009
Nantes Université
2008
Recent studies have suggested a close relationship between CD4(+)FOXP3(+) regulatory T cells (Tregs) and proinflammatory IL-17-producing helper (T(H)17) expressing the lineage-specific transcription factor RORgamma t. We report here unexpected finding that human memory Tregs secrete IL-17 ex vivo constitutively express IL-17-secreting share some phenotypic functional features with conventional T(H)17 cells, high levels of CCR4 CCR6 low CXCR3. However, unlike they CD161 mostly fail to...
Chronic GVHD (cGVHD) is the major cause of late, nonrelapse death following stem cell transplantation and characteristically develops in organs such as skin lung. Here, we used multiple murine models cGVHD to investigate contribution macrophage populations development cGVHD. Using an established IL-17-dependent sclerodermatous model, confirmed that macrophages infiltrating are derived from donor bone marrow (F4/80+CSF-1R+CD206+iNOS-). Cutaneous developed a CSF-1/CSF-1R-dependent manner,...
Natural regulatory T cells (nTregs) play an important role in tolerance; however, the small numbers of obtainable potentially limit feasibility clinical adoptive transfer. Therefore, we studied and efficacy using murine-induced (iTregs) for induction tolerance after bone marrow transplantation. iTregs could be induced large from conventional donor CD4 CD8 within 1 wk were highly suppressive. During graft-versus-host disease (GVHD), suppressed proliferation effector production proinflammatory...
The primacy of the gastrointestinal (GI) tract in dictating outcome graft-versus-host disease (GVHD) is broadly accepted; however, mechanisms controlling this effect are poorly understood. Here, we demonstrate that GVHD markedly enhances alloantigen presentation within mesenteric lymph nodes (mLNs), mediated by donor CD103+CD11b− dendritic cells (DCs) migrate from colon under influence CCR7. Expansion and differentiation T specifically mLNs driven profound levels alloantigen, IL-12, IL-6...
Background Pixatimod is a unique activator of the Toll-like Receptor 9 pathway. This phase I trial evaluated safety, efficacy and pharmacodynamics pixatimod PD-1 inhibitor nivolumab in immunologically cold cancers. Methods 3+3 dose escalation with microsatellite stable metastatic colorectal cancer (MSS mCRC) pancreatic ductal adenocarcinoma (mPDAC) expansion cohorts. Participants received once weekly as 1-hour intravenous infusion plus every 2 weeks. Objectives included assessment antitumor...
Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects Tregs result diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), serious complication allogeneic stem cell transplantation (SCT). We recently reported increased expression autophagy-related genes (Atg) association with enhanced survival after SCT. Autophagy is self-degradative process for cytosolic components that promotes...
Epithelial ovarian cancer (EOC) is a highly inflammatory malignancy, characterized by the presence, at tumor site, of regulatory T cells (Treg) that suppress antitumor immunity. Recently, new lineage CD4+ producing proinflammatory cytokine interleukin (IL)-17 [T helper (TH) 17] has been identified as major player in some autoimmune diseases. The role TH17 cancer, however, and their relationship with coexisting Treg populations, whose differentiation partially controlled same mediators (ie,...
Abstract The stimulation of naive donor T cells by recipient alloantigen is central to the pathogenesis graft-versus-host disease after bone marrow transplantation (BMT). Using mouse models transplantation, we have observed that become “cross-dressed” in very high levels hematopoietic cell–derived MHC class I and II molecules following BMT. Recipient-type transiently present on dendritic (DCs) BMT setting myeloablative conditioning but persistent nonmyeloablative conditioning, which remain...
Abstract The majority of allogeneic stem cell transplants are currently undertaken using G-CSF mobilized peripheral blood cells. has diverse biological effects on a broad range cells and IL-10 is key regulator many these effects. Using mixed radiation chimeras in which the hematopoietic or nonhematopoietic compartments were wild-type, IL-10−/−, G-CSFR−/−, combinations thereof we demonstrated that attenuation alloreactive T responses after mobilization required direct signaling by both IL-10....
Abstract Autophagy is an intracellular survival process that has established roles in the long-term and function of hematopoietic stem cells (HSC). We investigated contribution autophagy to HSC fitness during allogeneic transplantation graft-versus-host disease (GVHD). demonstrate vitro both tumor necrosis factor IL-1β, major components GVHD cytokine storm, synergistically promote their more mature progenitor (HPC). In vivo we increased donor HPC GVHD. Competitive transplant experiments...
During gestation, maternal cells traffic to the fetus leading natural phenomenon of microchimerism. Although their persistence in offspring has been associated with several autoimmune disorders, precise role these disorders remains unclear. We aimed evaluate whether alloreactive T could directly trigger a graft-vs.-host like reaction or indirectly influence development offspring's regulatory (Treg) favoring autoimmunity. In specific breeding strategy, we recently reported that allogeneic...
The origins of autoimmunity are still elusive despite significant advances in immunology. There is cumulative evidence that, beyond simple genetics, the maternal environment plays a critical role development common autoimmune disorders, such as multiple sclerosis or diabetes. In recent years, trafficking cells to offspring has been clearly demonstrated. This microchimerism represents very first immunological event fetal life. number persisting associated with several disorders systemic...
The origins of autoimmunity are still elusive despite significant advances in immunology. There is cumulative evidence that, beyond simple genetics, the maternal environment plays a critical role development common autoimmune disorders, such as multiple sclerosis or diabetes. In recent years, trafficking cells to offspring has been clearly demonstrated. This microchimerism represents very first immunological event fetal life. number persisting associated with several disorders systemic...
Abstract The role of trogocytosis in generating naïve T cell responses is controversial and highly relevant to transplantation. We transplanted B6.CD11cGFP donor bone marrow (BM) grafts (H2Db, IAb, GFP off the CD11c promoter) into irradiated B6D2F1 (H2Db/d, IAb/d,) tracked DC. Using standard imaging flow cytometry, we noted that all cells become “cross-dressed” high levels recipient hematopoietic cell-derived MHC early after BMT. To assess functional consequences cross-dressed MHC,...