A5052497081- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Cancer Immunotherapy and Biomarkers
- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Biosimilars and Bioanalytical Methods
- Polyomavirus and related diseases
- Endoplasmic Reticulum Stress and Disease
- Multiple Sclerosis Research Studies
- Protein purification and stability
- Protein Tyrosine Phosphatases
- Biochemical and Molecular Research
- T-cell and Retrovirus Studies
- Electromagnetic Compatibility and Noise Suppression
- Heat shock proteins research
- Plant Virus Research Studies
- Cutaneous lymphoproliferative disorders research
- Viral-associated cancers and disorders
- Autoimmune Bullous Skin Diseases
Harvard University
2003-2024
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2003-2024
Biogen (United States)
2011-2021
C4 Therapeutics (United States)
2021
Boston Children's Hospital
2009-2019
Tokushima Bunri University
2006
Immune Regulation (United Kingdom)
2006
University of Birmingham
2006
University of Milano-Bicocca
2006
University of Washington
1996-2001
Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic (DC) GALT induce T cell-independent expression of IgA and gut-homing receptors on cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote secretion. However, RA potently synergized with interleukin-6 (IL-6) or IL-5 to Consequently, mice deficient the precursor vitamin lacked...
A B lymphocyte hyperactivity syndrome resembling systemic lupus erythematosus characterizes mice lacking the src-family kinase Lyn. Lyn is not required to initiate cell antigen receptor (BCR) signaling but an essential inhibitory component. lyn−/− cells have a delayed increased calcium flux and exaggerated negative selection responses in presence of spontaneous absence antigen. As invertebrates, genetic effects loci with only one functional allele can be used analyze networks mice,...
Type I interferons (IFN-I) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). In SLE, immune complexes bind to CD32a (FcγRIIa) receptor on surface plasmacytoid dendritic cells (pDCs) and stimulate secretion IFN-I from pDCs. BDCA2 is a pDC-specific that, when engaged, inhibits production human engagement, therefore, represents an attractive therapeutic target for inhibiting pDC-derived may be effective therapy treatment SLE. this study, we show that 24F4A, humanized...
B1 or B2? The BCR decides Immunological B cells are generally divided into two major subsets. B2 generate specific antibodies against foreign antigens in secondary lymphoid organs. cells, found predominantly the peritoneal and pleural cavities, instead produce “natural” as part of innate immune system. Two models to explain this split exist: “lineage model,” wherein both subsets have distinct progenitors, “selection which fates directed by different cell antigen receptors (BCRs). Graf et al....
In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development the pre-B stage. A subsequent functional light (LC) then results surface expression of IgM at immature cell Here we show that interruption basal signaling cells, either by inducible deletion Ig via Cre-mediated excision or incubating with tyrosine kinase inhibitor herbimycin phosphatidylinositol 3-kinase...
B cell activating factor (BAFF) signals through BAFF-R to promote mature survival. Recent analyses of BAFF-induced signaling revealed direct association between augmented metabolic fitness and activation Akt, one the key regulators The strongest most reproducible induction Akt occurs with significant delay (24 h) after BAFF treatment, where it precedes anabolism. It was also recently shown that induces sustained Erk increased turnover proapoptotic molecule Bim. Here we show these pathways...
To assess if the percentage of CD3(+)CD4(+)CD62L(+) cells in cryopreserved peripheral blood mononuclear (PBMCs) (here termed %CD62L) can predict risk developing progressive multifocal leukoencephalopathy (PML) and better inform physician for benefit-risk assessment natalizumab treatment decisions a global setting.Cryopreserved PBMCs from 21 natalizumab-treated patients who developed PML 104 matched with multiple sclerosis (MS) without collected as part Biogen clinical trials were...
Multiple Sclerosis is a chronic autoimmune neurodegenerative disorder of the central nervous system (CNS) that characterized by inflammation, demyelination, and axonal injury leading to permeant disability. In early stage MS, inflammation primary driver disease progression. There remains an unmet need develop high efficacy therapies with superior safety profiles prevent processes Herein, we describe discovery BIIB091, structurally distinct orthosteric ATP competitive, reversible inhibitor...
Autoreactive B cell-derived antibodies form immune complexes that likely play a pathogenic role in autoimmune diseases. In systemic lupus erythematosus (SLE), these bind Fc receptors on myeloid cells and induce proinflammatory cytokine production by monocytes NETosis neutrophils. Bruton's tyrosine kinase (BTK) is non-receptor signals downstream of plays transduction antibody expression following cell activation. Given the roles BTK both sensing autoreactive antibodies, inhibitors activity...
Significance Clonal expansion of antigen-specific B cells during an immune response is necessary for effective antibody production. must integrate signals from their clonally restricted B-cell antigen receptor (BCR) and nonclonal coreceptors that provide contextual cues to the nature antigen. How this accomplished unclear. We found require expression BCR mitogenic responses triggered by recognize innate or T-cell-derived signals. The signaling pathway used license coreceptor-induced...
Abstract MK-6194, an interleukin-2 mutein designed to selectively activate regulatory T cells (Tregs), was evaluated for safety, pharmacokinetics (PK), immunogenicity, and pharmacodynamics in healthy participants. In a single ascending dose trial (N = 56), participants received subcutaneous MK-6194 or placebo (3:1 ratio) across levels ranging from 1 10 mg. multiple 54), at 0.5 5 mg every 2 wk (total 3 doses) as well 4 doses). Baseline characteristics were comparable between trials, with...
Abstract Background and purpose: BTK mediates B-cell receptor signaling was validated as a target by the inhibitor ibrutinib in several malignancies, including mantle cell lymphoma chronic lymphocytic leukemia (CLL). However, patients may have or acquire resistance. Resistance mechanisms include mutation of cysteine active site that requires for covalent binding (C481). We identified characterized SNS-062, potent, noncovalent with activity towards harboring resistance mutations also inhibits...
Regulatory T (Treg) cells are essential to maintain immune homeostasis in the intestine and Treg cell dysfunction is associated with several inflammatory autoimmune disorders including bowel disease (IBD). Efforts using low-dose (LD) interleukin-2 (IL-2) expand autologous show therapeutic efficacy for conditions. Whether LD IL-2 an effective strategy treating patients IBD unknown. Recently, we demonstrated that was protective against experimental colitis humanized mice which human CD4+ were...
Background: Regulatory T cells (Tregs) play a critical role in immune homeostasis and are dysfunctional many autoimmune diseases. Interleukin 2 (IL-2) drives the proliferation function of Tregs. via heterotrimeric IL-2 receptor (CD25/CD122/CD132). As result, CD25 loss-of-function mice is associated with Treg deficiency widespread autoimmunity. Low dose being evaluated for treatment diseases has been shown to expand Tregs, however it narrow selectivity window before activating conventional...
Abstract Igα serine 191 and 197 threonine 203, which are located in proximity of the ITAM, dampen ITAM tyrosine phosphorylation. In this study, we show that mice with targeted mutations S191, 197, T203 displayed elevated serum IgG2c IgG2b concentrations had numbers IgG2c- IgG2b-secreting cells bone marrow. BCR-induced phosphorylation was slightly increased splenic B cells. Our results suggest serine/threonines limit formation marrow plasma cells, possibly by fine-tuning tyrosine-mediated BCR...