A5077197953- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- COVID-19 Clinical Research Studies
- Developmental Biology and Gene Regulation
- Immune Response and Inflammation
- Long-Term Effects of COVID-19
- Psoriasis: Treatment and Pathogenesis
- Inflammasome and immune disorders
- Monoclonal and Polyclonal Antibodies Research
- Electrostatic Discharge in Electronics
- Plasma Diagnostics and Applications
- Dermatology and Skin Diseases
- Immunodeficiency and Autoimmune Disorders
Harvard University
2006-2023
Sunnybrook Research Institute
2015-2018
Sunnybrook Health Science Centre
2014-2018
University of Toronto
2014-2018
The University of Texas at Austin
2006
Tregs have the potential to establish long-term immune tolerance in patients recently diagnosed with type 1 diabetes (T1D) by preserving β cell function. Adoptive transfer of autologous thymic Tregs, although safe, exhibited limited efficacy previous T1D clinical trials, likely reflecting a lack tissue specificity, IL-2 signaling support, and vivo plasticity Tregs. Here, we report engineering strategy using bulk CD4+ T cells generate Treg therapy (GNTI-122) that stably expresses FOXP3,...
Antibody class switching in activated B cells uses switch recombination (CSR), which joins activation-induced cytidine deaminase (AID)-dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus (S) regions that lie up to 200 kilobases apart. To test postulated roles of S and AID CSR, we generated mutant donor Smu accepter Sgamma1 were replaced with yeast I-SceI endonuclease sites. We found site-specific DSBs mediate recombinational IgH from IgM IgG1 without...
IL-17-producing γδ T (γδT17) cells are critical components of the innate immune system. However, gene networks that control their development unclear. Here we show HEB (HeLa E-box binding protein, encoded by Tcf12) is required for generation a newly defined subset fetal-derived CD73- γδT17 cells. in immature CD24+CD73- expression Sox4, Sox13, and Rorc, these genes repressed acute antagonist Id3. HEB-deficiency also affects mature CD73+ cells, which defective RORγt IL-17 production....
Unlike αβ-T lineage cells, where the role of ligand in intrathymic selection is well established, development γδ-T cells remains controversial. Here we provide evidence for a bona fide selecting shaping cell-receptor (TCR) repertoire. Reactivity γδ-TCR with major histocompatibility complex (MHC) Class Ib ligands, H2-T10/22, critically dependent upon EGYEL motif complementarity determining region 3 (CDR3) TCRδ. In absence H2-T10/22 ligand, commitment reactive to γδ fate diminished, and...
Significance Expression of a productively rearranged T-cell receptor (TCR)-β chain induces program αβ T-lineage differentiation, whereas thymocytes that TCR-γ and TCR-δ typically give rise to γδ-lineage T cells. However, given all three TCR gene loci simultaneously undergo rearrangements, the possibility exists developing thymocyte may express γδ-TCR together with TCR-β or pre-TCR complex, it is not clear what this outcome would in terms differentiation. Our findings point striking...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes disease 2019 (COVID-19), a lung that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors progressive would allow for therapeutic intervention those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated either arbidol (ARB) or inhaled interferon (IFN)-α2b +/−ARB. IFN treatment resulted accelerated viral clearance from upper...
Izumo1R is a pseudo-folate receptor with an essential role in mediating tight oocyte/spermatozoa contacts during fertilization. Intriguingly, it also expressed CD4 + T lymphocytes, particular Treg cells under the control of Foxp3. To understand function cells, we analyzed mice Treg-specific Izumo1r deficiency (Iz1rTrKO). differentiation and homeostasis were largely normal, no overt autoimmunity only marginal increases PD1 CD44 hi phenotypes. pTreg was unaffected. Iz1rTrKO proved uniquely...
γδ T-cells perform a wide range of tissue- and disease-specific functions that are dependent on the effector cytokines produced by these cells. However, aggregate signals required for development interferon-γ (IFNγ) interleukin-17 (IL-17) producing remain unknown. Here, we define cues involved in functional programming T-cells, examining roles T-cell receptor (TCR), Notch, cytokine-receptor signaling. KN6 γδTCR-transduced Rag2-/- progenitors were cultured stromal cells variably expressing...
Abstract FOXP3 +Regulatory T cells (Tregs) play a critical role in the prevention of fatal autoimmunity and maintaining tissue homeostasis. The functional stability Tregs remains their contribution towards immune tolerance rather than runaway immunity, particularly for cell therapy whereby an inflammatory microenvironment may impact expression associated tolerogenic genes. To address potential Treg instability, we generated human Engineered (EngTregs) through gene editing approach PBMC...