A5055943543- Diabetes and associated disorders
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Pancreatic function and diabetes
- Diabetes Management and Research
- Immunotherapy and Immune Responses
- Atherosclerosis and Cardiovascular Diseases
- Diabetes Treatment and Management
- Single-cell and spatial transcriptomics
- Proteoglycans and glycosaminoglycans research
- Gestational Diabetes Research and Management
- CAR-T cell therapy research
- Bariatric Surgery and Outcomes
- Protein Tyrosine Phosphatases
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- Functional Brain Connectivity Studies
- Vascular Procedures and Complications
- Hematopoietic Stem Cell Transplantation
- Traumatic Brain Injury Research
- Galectins and Cancer Biology
- Pregnancy and preeclampsia studies
- Phytochemical compounds biological activities
- Childhood Cancer Survivors' Quality of Life
- Long-Term Effects of COVID-19
Benaroya Research Institute
2016-2025
Hangzhou Normal University
2025
Harbin Engineering University
2025
Virginia Mason Medical Center
2013-2024
Seattle University
2010-2024
University of Florida
2021-2023
Graceland University
2023
Mothers’ Milk Bank
2023
Purdue University West Lafayette
2023
The Ohio State University
2023
Autologous regulatory T cells can be expanded and are well tolerated in patients with recent-onset type 1 diabetes.
Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss production in patients with type diabetes, but might affect clinical progression before diagnosis are needed.We conducted phase 2, randomized, placebo-controlled, double-blind trial teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives who did not were at high risk...
Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects rapamycin/IL-2 therapy in type diabetic (T1D) patients. Nine T1D subjects were treated with 2–4 mg/day rapamycin orally for 3 months 4.5 × 106 IU IL-2 s.c. three times per week month. β-Cell function was monitored by measuring C-peptide. Immunologic changes using flow cytometry serum analyses. Regulatory T...
The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility complex; rates progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, therapeutic intervention efficacy vary widely. Mechanistic...
In humans, multiple genes in the interleukin (IL)-2/IL-2 receptor (IL-2R) pathway are associated with type 1 diabetes. However, no link between IL-2 responsiveness and CD4(+)CD25(+)FOXP3(+) regulatory T-cells (Tregs) has been demonstrated diabetic subjects despite role of these IL-2-dependent cells controlling autoimmunity. Here, we address whether altered impacts persistence FOXP3 expression Tregs subjects.Persistence was assessed by culturing sorted CD4(+)CD25(hi) natural measuring over...
BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes prolonged preservation endogenous insulin secretion remaining patients with newly diagnosed T1D.
Teplizumab treatment of nondiabetic relatives at high risk for T1D induces partially exhausted CD8 + T cells and improves beta cell function.
Biologic treatment of T1D typically results in transient stabilization C-peptide levels (a surrogate for endogenous insulin secretion) some patients, followed by progression at the same rate as untreated control groups. Here, we used integrated systems biology and flow cytometry approaches with clinical trial blood samples to elucidate pathways associated subjects treated anti-CD3 monoclonal antibody teplizumab. We identified a population CD8 T cells that accumulated best response...
Human blood and lymph contain circulating CD4 + CD103 cutaneous resident memory T cells that can seed distant skin sites. See the related Focus by Carbone Gebhardt .
OBJECTIVE Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of diabetes from normal glucose tolerance (NGT) to abnormal (AGT) and the effects treatment on immune metabolic responses. RESEARCH DESIGN AND METHODS conducted a phase 2, randomized, placebo-controlled, double-masked trial antibody-positive participants NGT who received...
The collapse of an initially spherical cavitation bubble near a free surface leads to the formation two jets: downward jet into liquid, and upward penetrating surface. In this study, we examine surprising interaction trapped in stable cavitating vortex ring approaching As result, single fast tall liquid forms. We find that is observed only above critical Froude numbers ( $Fr$ ) Weber $We$ when ${Fr}^2 (1.6-2.73/{We}) > 1$ , illustrating importance inertia, gravity tension accelerating...
Work by our group and others has demonstrated a role for the extracellular matrix receptor CD44 its ligand hyaluronan in CD4(+)CD25(+) regulatory T cell (Treg) function. Herein, we explore mechanistic basis this observation. Using mouse FoxP3/GFP(+) Treg, find that costimulation promotes expression of FoxP3, part through production IL-2. This promotion IL-2 was resistant to cyclosporin A treatment, suggesting may promote bypassing FoxP3-mediated suppression NFAT. increased IL-10 partially...
Effector T cells in patients with active RRMS can be resistant to immune tolerance through a mechanism involving IL-6R signaling.
We describe a role for ECM as biosensor inflammatory microenvironments that plays critical in peripheral immune tolerance. show hyaluronan (HA) promotes induction of Foxp3- IL-10-producing regulatory T cells (TR1) from conventional T-cell precursors both murine and human systems. This is, to our knowledge, the first description an component inducing cells. Intact HA, characteristic healing tissues, TR1 capable abrogating disease IL-10-dependent mouse colitis model whereas fragmentary typical...
Although most patients with type 1 diabetes (T1D) retain some functional insulin-producing islet β cells at the time of diagnosis, rate further cell loss varies across individuals. It is not clear what drives this differential progression rate. CD8+ T have been implicated in autoimmune destruction cells. Here, we addressed whether phenotype and function autoreactive influence disease progression. We identified islet-specific using high-content, single-cell mass cytometry combination...
IL-2 receptor (IL-2R) signaling is essential for optimal stability and function of CD4+CD25hiFOXP3+ regulatory T cells (Treg); a cell type that plays an integral role in maintaining tolerance. Thus, we hypothesized decreased response to may be common phenotype subjects who have autoimmune diseases associated with variants the IL2RA locus, including T1D MS, particularly expressing high affinity IL-2R alpha chain (IL-2RA or CD25). To examine this question used phosphorylation STAT5 (pSTAT5) as...
A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA1c for year in new-onset type diabetes. Subjects (N = 89) were randomized to 1) ATG pegylated granulocyte colony-stimulating factor (GCSF), 2) alone, or 3) placebo. Herein, we report 2-year area under curve (AUC) C-peptide HbA1c, prespecified...
T cells from diabetic individuals are hyperresponsive to IL-6 stimulation, which could contribute disease pathogenesis and may be an avenue for therapeutic intervention.
BackgroundType 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, preclinical studies show that it reverses prevents diabetes. Our aim was to evaluate the safety efficacy in preserving β-cell function patients with recent-onset type diabetes.MethodsWe did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients (<100 days diagnosis), aged 18–45...
Permutational analysis of the immune system reveals advanced aging in individuals with Down syndrome and type 1 diabetes.