A5088600292- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Eosinophilic Esophagitis
- Immune cells in cancer
- Immune Response and Inflammation
- Mast cells and histamine
- Asthma and respiratory diseases
- Tissue Engineering and Regenerative Medicine
- Cytokine Signaling Pathways and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- Transplantation: Methods and Outcomes
- Chemokine receptors and signaling
- Hematopoietic Stem Cell Transplantation
- Organ Transplantation Techniques and Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Organ and Tissue Transplantation Research
- Immune responses and vaccinations
- Extracellular vesicles in disease
- Neuroinflammation and Neurodegeneration Mechanisms
University of Pittsburgh
2016-2025
McGowan Institute for Regenerative Medicine
2019-2024
University of Pittsburgh Medical Center
2019-2024
Anderson Orthopaedic Clinic
2021
UPMC Presbyterian
2019
Presbyterian Hospital
2019
GTx (United States)
2015
Children's Hospital of Pittsburgh
2014
Vanderbilt University
2014
H.C. Starck (Germany)
2009-2013
Abstract The ability of dendritic cells (DC) to regulate Ag-specific immune responses via their influence on T regulatory (Treg) may be key potential as therapeutic tools or targets for the promotion/restoration tolerance. In this report, we describe maturation-resistant, rapamycin (RAPA)-conditioned DC, which are markedly impaired in Foxp3− cell allostimulatory capacity, favor stimulation murine alloantigen-specific CD4+CD25+Foxp3+ Treg. This was distinct from control especially following...
IL-33 administration is associated with facilitation of Th2 responses and cardioprotective properties in rodent models. However, heart transplantation, the mechanism by which IL-33, signaling through ST2L (the membrane-bound form ST2), promotes transplant survival unclear. We report that administration, while facilitating responses, also increases immunoregulatory myeloid cells CD4(+) Foxp3(+) regulatory T (Tregs) mice. expands functional myeloid-derived suppressor cells, CD11b(+) exhibit...
Cancer immunotherapy has shown great promise as a new standard cancer therapeutic modality. However, the response rates are limited for current approach that depends on enhancing spontaneous antitumor immune responses. Therefore, increasing tumor immunogenicity by expressing appropriate cytokines should further improve immunotherapy. IL-33 is member of IL-1 family and released necrotic epithelial cells or activated innate thus considered "danger" signal. The role in promoting type 2...
IL-33 is a recently characterized IL-1 family member that proposed to function as an alarmin, or endogenous signal of cellular damage, well act pleiotropic cytokine. The ability potentiate both Th1 and Th2 immunity supports its role in pathogen clearance disease immunopathology. Yet, restrains experimental colitis transplant rejection by expanding regulatory T cells (Treg) via undefined mechanism. We sought determine the influence on hematopoietic drives Treg expansion underlies therapeutic...
Abstract The effector functions of CD8 + T cells are influenced by tissue inflammatory microenvironments. IL‐33, a member the IL‐1 family, acts as danger signal after its release during cell necrosis. IL‐33/ST2 axis has been implicated in various Th2 responses. Its role T‐cell‐mediated immune response is, however, not known. Here we find that type 1 cytotoxic (Tc1) cultured vitro unexpectedly express high levels IL‐33 receptor ST2. Interestingly, expression ST2 Tc1 is dependent on T‐bet,...
Innate immune cells remember Immunological memory is a phenomenon by which can quickly recognize an antigen that the host has previously encountered. Certain of innate system exhibit memory-like responses know as trained immunity. Rapid, antigen-specific secondary (anamnestic) were long thought to be domain B and T cells. However, Dai et al. report monocytes macrophages acquire specific for particular major histocompatibility complex I antigens using paired A-type immunoglobulin-like...
Background The immunosuppression and immune dysregulation that follows severe injury includes type 2 responses manifested by elevations in interleukin (IL) 4, IL5, IL13 early after injury. We hypothesized IL33, an alarmin released tissue a known regulator of immunity, contributes to the systemic Methods findings Blunt trauma patients admitted intensive care unit level I center were enrolled observational study included frequent blood sampling. Dynamic changes IL33 soluble suppression...
Acute respiratory distress syndrome is an often fatal disease that develops after acute lung injury and trauma. How released tissue damage signals, or alarmins, orchestrate early inflammatory events poorly understood. Herein we reveal IL-33, alarmin sequestered in the epithelium, required to limit inflammation due unappreciated capacity mediate Foxp3+ Treg control of local cytokines myeloid populations. Specifically, Il33-/- mice are more susceptible damage-associated morbidity mortality...
Alarmins, sequestered self-molecules containing damage-associated molecular patterns, are released during tissue injury to drive innate immune cell proinflammatory responses. Whether endogenous negative regulators controlling early responses also at the site of is poorly understood. Herein, we establish that stromal cell–derived alarmin interleukin 33 (IL-33) a local factor directly restricts capacity graft-infiltrating macrophages after transplantation. By assessing heart transplant...
Abstract Intestinal stem cells (ISCs) maintain the epithelial lining of intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as biomarker, regulates intrinsic regeneration by inducing production epidermal growth factor (EGF). Three-dimensional imaging lineage-specific RiboTag induction...
Abstract Maturation resistance and tolerogenic properties can be conferred on human murine dendritic cells (DC), crucial regulators of T cell responses, by exposure to rapamycin (RAPA), a “tolerance-sparing” immunosuppressive agent. Mechanisms underlying this acquired unresponsiveness, typified diminished functional responses TLR or CD40 ligation, have not been identified. We report that in vitro vivo conditioning myeloid DC with RAPA elicits the de novo production IL-1β otherwise...
Chromatin-modifying HDACi exhibit anti-inflammatory properties that reflect their ability to suppress DC function and enhance regulatory T cells. The influence of on MDSCs, an emerging leukocyte population potently inhibits cell proliferation, has not been examined. Exposure GM-CSF-stimulated murine BM cells led a robust expansion monocytic MDSC (CD11b(+)Ly6C(+)F4/80(int)CD115(+)), which suppressed allogeneic proliferation in NOS- HO-1-dependent manner with similar potency control MDSCs....
Significance Vascularized composite allotransplantation (VCA) is an emerging field that particularly beneficial for select amputees and patients with devastating soft tissue loss not amenable to conventional reconstructive surgeries. As solid organ transplantation, VCA recipients are subjected a lifelong regimen of antirejection drugs well-established sequela. Herein, we report synthetic, controlled-release microparticle system (referred as TRI-MP) aims locally enrich naturally occurring,...