A5103002681- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Multiple Sclerosis Research Studies
- Immune Response and Inflammation
- interferon and immune responses
- HIV Research and Treatment
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- MicroRNA in disease regulation
- Polyomavirus and related diseases
- Bone Metabolism and Diseases
- Biomarkers in Disease Mechanisms
- Digestive system and related health
- NF-κB Signaling Pathways
- Cancer-related molecular mechanisms research
- Acute Lymphoblastic Leukemia research
- Extracellular vesicles in disease
- Cytokine Signaling Pathways and Interactions
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- CAR-T cell therapy research
- IL-33, ST2, and ILC Pathways
University of California, San Francisco
2017-2023
Institute of Biomedical Science
2023
McGill University
2023
Amgen (United States)
2019-2023
Harvard University
2023
Shandong Normal University
2023
Boston Children's Hospital
2023
University of Würzburg
2021
Ningbo First Hospital
2019-2020
Oregon Health & Science University
2017
Abstract The transcriptional repressor Bcl6 controls development of the follicular Th cell (TFH) lineage, but precise mechanisms by which regulates this process are unclear. A model has been proposed whereby represses differentiation T cells into alternative effector lineages, thus favoring TFH differentiation. Analysis using Bcl6-deficient mice complicated strong proinflammatory phenotype myeloid cells. In study, we report data from a novel mouse where is conditionally deleted in...
A role of B cells in multiple sclerosis (MS) is well established, but there limited understanding their involvement during active disease. Here, we examined cerebrospinal fluid (CSF) and peripheral blood (PB) treatment-naive patients with MS or high-risk clinically isolated syndrome. Using flow cytometry, found increased CSF lymphocytes a disproportionate increase compared T gadolinium-enhancing (Gd+) lesions on brain MRI. Ig gene heavy chain variable region (Ig-VH) repertoire sequencing PB...
The importance of follicular T helper (TFH) cells and the germinal center (GC) reaction in humoral immune response has become clear recent years, however role TFH GC an HIV vaccine strategy remains unclear. In this study, we primed mice with gp120-encoding DNA boosted gp120 protein, a regimen previously shown to induce high titers affinity cross-reactive anti-gp120 Abs. Priming caused increased cell differentiation, B cells, antigen-specific antibody titers, compared priming protein. also...
Abstract The transcription factor Bcl6 is required for development of follicular helper T (TFH) cells. Cytokines that activate Stat3 promote expression and TFH cell differentiation. Previous studies with an acute virus infection model showed differentiation was decreased but not blocked in the absence Stat3. In this study, we further analyzed role Peyer’s patches, found compared wild-type, Stat3-deficient cells developed at a 25% lower rate expressed increased IFN-γ IL-4. Whereas patch...
B cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related exist the cerebrospinal fluid (CSF), meninges, and CNS parenchyma of MS patients. We sought investigate presence clonally over time by performing Ig heavy chain variable region repertoire sequencing on from longitudinally collected blood CSF samples patients (n = 10). All were untreated at initial sampling; majority 7) treated with immune-modulating therapies 1.2 (±0.3 SD) years later...
Foxp3(+) regulatory T (Treg) cells are essential to maintain immune homeostasis, yet controversy exists about the stability of this cell population. Bcl6-deficient (Bcl6(-/-) ) mice develop severe and spontaneous helper type 2 (Th2) inflammation Treg ineffective at controlling Th2 responses. We used a lineage tracing approach analyse fate in these mice. In periphery Bcl6(-/-) mice, increased numbers Foxp3-negative 'exTreg' were found, particularly CD25(+) ExTreg from expressed interleukin-17...
PU.1 is an ETS family transcription factor that important for the development of multiple hematopoietic cell lineages. Previous work demonstrated a critical role in promoting Th9 and limiting Th2 cytokine production. Whether has functions other Th lineages not clear. In this study, we examined effects ectopic expression CD4(+) T cells observed decreased genes involved with function follicular helper (Tfh) cells, including Il21 Tnfsf5 (encoding CD40L). from conditional mutant mice lack...
Objectives: The mechanism and immunoregulatory role of natural killer (NK) cells in human graft-versus-host-disease (GVHD) remains unclear. This study quantitatively analyzed the cytotoxicity donor NK towards alloreactive T cells, investigated their relationship with acute GVHD (aGVHD). Methods: We evaluated dose, subgroup, receptor expression allografts from 98 patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). A CD107a degranulating assay was used as a...
The B cell-depleting anti-CD20 antibody ocrelizumab (OCR) effectively reduces MS disease activity and slows disability progression. Given the role of cells as antigen-presenting cells, primary goal this study was to evaluate effect OCR on T-cell receptor repertoire diversity.
The therapeutic expansion of Foxp3 + regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity function Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 from mice treated with a half-life extended mutant form murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as control. Cell clustering analysis revealed IL-2M specifically expands multiple...
Interleukin-2 (IL-2), along with T-cell receptor (TCR) signaling, are required to control regulatory T cell (Treg) homeostasis and function in vivo. Due the heightened sensitivity IL-2, Tregs retain ability respond low-dose or attenuated forms of as currently being developed for clinical use treat inflammatory diseases. While IL-2 increases Treg selectivity, question remains whether a weakened signal sufficiently enhances suppressive function(s) toward disease modification. To understand...
Abstract Background Graft-versus-host disease (GVHD) is one of the most complex complications after allogeneic stem cell transplantation. Current standard grading system based on clinical symptoms in skin, liver and intestinal. However, it’s difficult to differ GVHD its extent just by manifestation. Here we retrospectively analyzed immune function patients implemented transplantation Ningbo first Hospital from Jan 2013 2018. Results data are collected 51 (mean age was 42; 45.1% women). The...
T cell activation and differentiation is associated with metabolic reprogramming to cope the increased bioenergetic demand provide intermediates for biosynthesis of building blocks. Antigen receptor stimulation not only promotes switch lymphocytes but also triggers uptake calcium (Ca2+) from cytosol into mitochondrial matrix. Whether Ca2+ influx through uniporter (MCU) controls metabolism effector function remained, however, enigmatic. Using mice cell-specific deletion MCU, we here show that...
The type-I interferon (IFN-I) signaling pathway is the first line of antiviral innate immunity. It must be precisely regulated against virus-induced damage. tightly mechanisms action host genes in immune are still worth studying. Here, we report a novel role DLG1 positively regulating IκB kinase epsilon (IKKε)-mediated IFN-I response negative-stranded RNA virus replication, whereas inhibits expression for escape. Importantly, E3 ligase March2 interacts with and promotes K27-linked...
Abstract The therapeutic expansion of Foxp3 + regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity function Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 from mice treated with a half-life extended mutant form murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as control. Cell clustering analysis revealed IL-2M specifically expands...
Abstract B-cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related exist the cerebrospinal fluid (CSF), meninges, and central nervous system (CNS) parenchyma of MS patients. Longitudinally stable CSF oligoclonal band (OCB) antibody patterns suggest some local CNS B-cell persistence; however, longitudinal dynamics within between blood remain unknown. We sought address this by performing immunoglobulin heavy chain variable region repertoire...