A5080920157- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Rheumatoid Arthritis Research and Therapies
- Immune cells in cancer
- Diabetes and associated disorders
- Psoriasis: Treatment and Pathogenesis
- Reproductive System and Pregnancy
- Gut microbiota and health
- HER2/EGFR in Cancer Research
- Pancreatic function and diabetes
- interferon and immune responses
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Clostridium difficile and Clostridium perfringens research
- Phagocytosis and Immune Regulation
- RNA Interference and Gene Delivery
- Preterm Birth and Chorioamnionitis
- Erythrocyte Function and Pathophysiology
- NF-κB Signaling Pathways
- Chemokine receptors and signaling
Coherus BioSciences (United States)
2023-2024
Cambridge Scientific (United States)
2016-2024
Harvard University
1999-2017
GlaxoSmithKline (United Kingdom)
2015
GlaxoSmithKline (United States)
2014-2015
Boehringer Ingelheim (Germany)
2012
Massachusetts General Hospital
1999-2010
Joslin Diabetes Center
2007-2010
Center for Systems Biology
2010
Brigham and Women's Hospital
2000-2009
Abstract Rheumatoid arthritis (RA) is genetically associated with MHC class II molecules that contain the shared epitope. These may participate in disease pathogenesis by selectively binding arthritogenic peptides for presentation to autoreactive CD4+ T cells. The nature of Ag not known, but recent work has identified posttranslationally modified proteins containing citrulline (deiminated arginine) as specific targets IgG Ab response RA patients. To understand how might evoke an autoimmune...
Vertebrates typically harbor a rich gastrointestinal microbiota, which has coevolved with the host over millennia and is essential for several physiological functions, in particular maturation of immune system. Recent studies have highlighted importance single bacterial species, segmented filamentous bacteria (SFB), inducing robust T-helper cell type 17 (Th17) population small-intestinal lamina propria (SI-LP) mouse gut. Consequently, SFB can promote IL-17–dependent autoimmune responses,...
Several important events occur at the maternal-fetal interface, including generation of tolerance, remodeling uterine smooth muscle and its spiral arteries glands, placental construction. Fetal-derived extravillous trophoblasts come in direct contact with maternal decidual leukocytes. Macrophages represent ∼20% leukocytes this interface. In study, two distinct subsets CD14(+) macrophages (dMs) are found to be present first-trimester tissue, CD11c(HI) CD11c(LO). Gene expression analysis by...
Rheumatoid arthritis (RA) is a common autoimmune disease that afflicts the synovium of diarthrodial joints. The pathogenic mechanisms inciting this are not fully characterized, but may involve loss tolerance to posttranslationally modified (citrullinated) antigens. We have demonstrated modification leads selective increase in antigenic peptide affinity for major histocompatibility complex (MHC) class II molecules carry RA-associated shared epitope, such as HLA-DRB1*0401 (DR4). describe...
Regulatory T (Treg) cells that express the Foxp3 transcription factor are essential for lymphoid homeostasis and immune tolerance to self. Other nonimmunological functions of Treg cells, such as controlling metabolic function in adipose tissue, also emerging. originate primarily thymus, but can be elicited from conventional by vivo exposure low-dose antigen or homeostatic expansion activation presence TGFβ vitro. characterized a distinct transcriptional signature controlled part, not solely,...
IL-17-producing CD4(+)Th17 cells, CD8(+)Tc17 and γδ T cells play critical roles in the pathogenesis of autoimmune psoriasis. RORγt is required for differentiation Th17 expression IL-17. In this article, we describe a novel, potent, selective inverse agonist (TMP778), its inactive diastereomer (TMP776). This chemistry, first time to our knowledge, provides unique powerful set tools probe RORγt-dependent functions. TMP778, but not TMP776, blocked human Tc17 cell also acutely modulated IL-17A...
Abstract RNA interference is a mechanism of posttranscriptional gene silencing that functions in most eukaryotic cells, including human and mouse. Specific mediated by short strands duplex ∼21 nt length (termed small interfering or siRNA) target the cognate mRNA sequence for degradation. We demonstrate here RNAi can be used immune modulation targeting dendritic cell (DC) expression. Transfection DC with siRNA specific IL-12 p35 resulted potent suppression expression blockade bioactive p70...
Abstract T and B lymphocytes are developmentally functionally related cells of the immune system, representing two major branches adaptive immunity. Although originating from a common precursor, they play very different roles: contribute to drive cell-mediated immunity, whereas secrete Abs. Because their functional importance well-characterized differentiation pathways, ideal cell types with which understand how differences encoded at transcriptional level. there has been great deal interest...
Abstract Inhibitory receptors (IR) are a diverse group of cell surface molecules that modulate T activation, but there gaps in our knowledge the cell-extrinsic factors regulate their expression. The present study found vivo overexpression IL-27 mice led to increased expression PD-L1, LAG-3, TIGIT, and TIM-3. In vitro, TCR stimulation alone promoted multiple IRs, whereas induced PD-L1. However, combination intermediate resulted synergistic induction CTLA-4, TIGIT. vivo, infection with...
Significance Dynamics and interactions of immunocytes infiltrating the pancreas during natural progression autoimmune diabetes are largely unknown. The construction diabetes-prone nonobese diabetic mice with a panel fluorescent reporters that illume cells innate adaptive immune systems, combined intravital imaging pancreas, provide novel perspectives on process ballet between aggressive regulatory cells.
Background CD47 is a broadly expressed cell surface glycoprotein associated with immune evasion. Interaction the inhibitory receptor signal regulatory protein alpha (SIRPα), primarily on myeloid cells, normally serves to restrict effector function (eg, phagocytosis and homeostasis). CD47/SIRPα antagonists, commonly referred as ‘macrophage checkpoint’ inhibitors, are being developed cancer interventions. SRF231 an investigational fully human IgG 4 anti-CD47 antibody that currently under...
Abstract Although inflammatory mechanisms driving hepatocellular carcinoma (HCC) have been proposed, the regulators of anticancer immunity in HCC remain poorly understood. We found that IL27 receptor (IL27R) signaling promotes development vivo. High IL27EBI3 cytokine or IL27RA expression correlated with poor prognosis for patients HCC. Loss IL27R suppressed vivo two different models hepatocarcinogenesis. Mechanistically, signaling within tumor microenvironment restrains cytotoxicity innate...
The T cell hybridoma FS7-20, produced by the fusion of normal B10.BR cells to AKR thymoma BW5147, was found when stimulated with concanavalin A (Con A) produce lymphokines: interleukin 2 (IL 2), interferon-gamma (IFN gamma), macrophage-activating factor (MAF), Ia induction IaIF), and B helper X X). clones subclones FS7-20 varied dramatically in their ability these lymphokines, presumably because karyotypic variations. IL segregated independently from four other lymphokine activities;...
The ability to image and ultimately quantitate β-cell mass in vivo will likely have far reaching implications the study of diabetes biology, monitoring disease progression or response treatment, for drug development. Here, using animal models, we report on synthesis, characterization, intravital microscopic imaging properties a near-infrared fluorescent exendin-4 analogue with specificity GLP-1 receptor β cells (E4K12-Fl). agent demonstrated subnanomolar EC50 binding concentrations, high...
Foxp3 + regulatory T cells (Tregs) originate in the thymus, but Treg phenotype can also be induced peripheral lymphoid organs or vitro by stimulation of conventional CD4 with IL-2 and TGF-β. There have been divergent reports on suppressive capacity these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal levels, are uniquely defective activity, whereas control strains (B6g7) ex vivo Tregs mice all function normally. Most Treg-typical...
ABSTRACT Mice that lack the genes for IL-27, or IL-27 receptor, and infected with Toxoplasma gondii develop T cell-mediated pathology. Here, studies were performed to determine impact of endogenous on immune response T. in wild-type (WT) mice. Analysis mice revealed early production IL-27p28 by a subset Ly6C hi , inflammatory monocytes, sustained at sites acute chronic infection. Administration anti-IL-27p28 prior infection resulted an (day 5) increase levels macrophage granulocyte...
As the only cells capable of efficiently resorbing bone, osteoclasts are central mediators both normal bone remodeling and pathologies associates with excessive resorption. However, despite clear evidence interplay between surface in vivo, role substrate regulating osteoclast differentiation activation at a molecular level has not been fully defined. Here, we present first comprehensive expression profiles differentiated on authentic resorbable substrates. This analysis identified numerous...