Megan K. Levings
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View article: Label-free estimation of regulatory T cell activation markers using Raman spectroscopy with machine learning
Label-free estimation of regulatory T cell activation markers using Raman spectroscopy with machine learning Open
Regulatory T cells are a class of T lymphocytes which respond to activation signals by expanding their cell numbers, and whose culturing and expansion are of significant clinical interest. Cellular activation states are used to inform proc…
View article: Lactic acid improves Treg manufacturing and in vivo function
Lactic acid improves Treg manufacturing and in vivo function Open
Adoptive cell therapy using regulatory T cells (Tregs) is a promising approach to suppress immune responses in autoimmunity and transplantation, but it is challenging to expand pure and optimally suppressive cells. Lactic acid (LA) is asso…
View article: TYK2 inhibition enhances Treg differentiation and function while preventing Th1 and Th17 differentiation
TYK2 inhibition enhances Treg differentiation and function while preventing Th1 and Th17 differentiation Open
View article: Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation
Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation Open
Aims/hypothesis Type 1 diabetes is an autoimmune disease caused by immune-mediated destruction of insulin-producing pancreatic beta cells. Interestingly, individuals with long-standing type 1 diabetes have residual beta cells, suggesting t…
View article: Reproducible detection of antigen-specific T cells and Tregs via standardized and automated activation-induced marker assay workflows
Reproducible detection of antigen-specific T cells and Tregs via standardized and automated activation-induced marker assay workflows Open
SUMMARY Activation-induced marker (AIM) assays are a promising tool to track antigen-specific T cells, but methodological heterogeneity between research groups hinders their clinical utility. To evaluate AIM assay reproducibility, we condu…
View article: CCL22-expressing Stem Cell–derived Islet Grafts Recruit Regulatory T Cells in Mice
CCL22-expressing Stem Cell–derived Islet Grafts Recruit Regulatory T Cells in Mice Open
Background. Cell therapy using human donor or stem cell–derived islets (SC-islets) to replace lost insulin-producing beta (β) cells holds great promise for type 1 diabetes. Recruiting regulatory T cells (Treg) through chemokine signaling c…
View article: Armored human CAR T <sub>reg</sub> cells with PD1 promoter-driven IL-10 have enhanced suppressive function
Armored human CAR T <sub>reg</sub> cells with PD1 promoter-driven IL-10 have enhanced suppressive function Open
Regulatory T cell (T reg cell) therapy has been transformed through the use of chimeric antigen receptors (CARs). We previously found that human T reg cells minimally produce IL-10 and have a limited capacity to control innate immunity com…
View article: Cell therapy with human interleukin 10–producing ILC2s enhances islet function and inhibits allograft rejection
Cell therapy with human interleukin 10–producing ILC2s enhances islet function and inhibits allograft rejection Open
View article: A Germline Heterozygous Dominant Negative IKZF2 Variant Causing Syndromic Primary Immune Regulatory Disorder and ICHAD
A Germline Heterozygous Dominant Negative IKZF2 Variant Causing Syndromic Primary Immune Regulatory Disorder and ICHAD Open
View article: CAR Treg synergy with anti-CD154 promotes infectious tolerance and dictates allogeneic heart transplant acceptance
CAR Treg synergy with anti-CD154 promotes infectious tolerance and dictates allogeneic heart transplant acceptance Open
Successful allograft-specific tolerance induction would eliminate the need for daily immunosuppression and improve posttransplant quality of life. Adoptive cell therapy with regulatory T cells expressing donor-specific chimeric antigen rec…
View article: Evaluating Activated Regulatory T Cells as a Biomarker of Chronic Allograft Inflammation in Pediatric Kidney Transplant Recipients
Evaluating Activated Regulatory T Cells as a Biomarker of Chronic Allograft Inflammation in Pediatric Kidney Transplant Recipients Open
Background There is a need for noninvasive immunological biomarkers that can identify stable kidney allograft immune quiescence to inform individualized immunosuppression. Methods We conducted a cross‐sectional, pilot cohort study evaluati…
View article: Author response: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
Author response: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity Open
View article: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity Open
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome…
View article: Meeting Report: The Sixth International Sam Strober Workshop on Clinical Immune Tolerance
Meeting Report: The Sixth International Sam Strober Workshop on Clinical Immune Tolerance Open
View article: Author response: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
Author response: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity Open
View article: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity Open
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome…
View article: Tunable differentiation of human CD4+ and CD8+ T cells from pluripotent stem cells
Tunable differentiation of human CD4+ and CD8+ T cells from pluripotent stem cells Open
Allogeneic T cell therapies are a highly desirable option to circumvent the cost and complexity of using autologous T cells to treat diseases. Allogeneic CD8+ T cells can be made from pluripotent stem cells (PSCs), but deriving CD4+ T cell…
View article: Sex-biased human thymic architecture guides T cell development through spatially defined niches
Sex-biased human thymic architecture guides T cell development through spatially defined niches Open
Within the thymus, regulation of the cellular crosstalk directing T cell development depends on spatial interactions within specialized niches. To create a spatially defined map of tissue niches guiding human postnatal T cell development, …
View article: Improving Reliability of Immunological Assays by Defining Minimal Criteria for Cell Fitness
Improving Reliability of Immunological Assays by Defining Minimal Criteria for Cell Fitness Open
Human PBMC-based assays are often used as biomarkers for the diagnosis and prognosis of disease, as well as for the prediction and tracking of response to biological therapeutics. However, the development and use of PBMC-based biomarker as…
View article: 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility
3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility Open
Genome-wide association studies (GWAS) have identified genetic links to autoimmune disorders, but lack detail on causal elements. We generated 3D genomic datasets of promoter-focused Capture-C, Hi-C, ATAC-seq, and RNA-seq across 57 human c…
View article: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity Open
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome…
View article: Author response: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
Author response: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity Open
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome…
View article: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity Open
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome…
View article: Ustekinumab for type 1 diabetes in adolescents: a multicenter, double-blind, randomized phase 2 trial
Ustekinumab for type 1 diabetes in adolescents: a multicenter, double-blind, randomized phase 2 trial Open
View article: Adaptive immune responses to two-dose COVID-19 vaccine series in healthy Canadian adults ≥ 50 years: a prospective, observational cohort study
Adaptive immune responses to two-dose COVID-19 vaccine series in healthy Canadian adults ≥ 50 years: a prospective, observational cohort study Open
To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization a…
View article: CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation
CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation Open
Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR…
View article: Issue Information: Eur. J. Immunol. 4'24
Issue Information: Eur. J. Immunol. 4'24 Open
View article: Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes
Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes Open
View article: 1165. Longitudinal Evaluation of SARS-CoV-2 Antibody Response Using Dried Blood Spot Samples Following Vaccination with Three and Four Doses of mRNA-1273, BNT162b2 and/or ChAdOx1-S in Adults Aged 50 and Above: Interim Analysis from the PREVENT-COVID Study
1165. Longitudinal Evaluation of SARS-CoV-2 Antibody Response Using Dried Blood Spot Samples Following Vaccination with Three and Four Doses of mRNA-1273, BNT162b2 and/or ChAdOx1-S in Adults Aged 50 and Above: Interim Analysis from the PREVENT-COVID Study Open
Background Multiple combinations of COVID-19 vaccine regimens have been used in Canada throughout the SARS-CoV-2 immunization campaign. Studies evaluating the humoral immune response following COVID-19 vaccination in community dwelling old…
View article: First-in-human therapy with Treg produced from thymic tissue (thyTreg) in a heart transplant infant
First-in-human therapy with Treg produced from thymic tissue (thyTreg) in a heart transplant infant Open
Due to their suppressive capacity, regulatory T cells (Tregs) have attracted growing interest as an adoptive cellular therapy for the prevention of allograft rejection, but limited Treg recovery and lower quality of adult-derived Tregs cou…