A5015306366- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Neuroscience and Neuropharmacology Research
- Dermatology and Skin Diseases
- Psoriasis: Treatment and Pathogenesis
- Diabetes and associated disorders
- Cancer Immunotherapy and Biomarkers
- Inflammatory Bowel Disease
- Chemotherapy-related skin toxicity
- Olfactory and Sensory Function Studies
- Cell death mechanisms and regulation
- Salivary Gland Tumors Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Mycobacterium research and diagnosis
- Memory and Neural Mechanisms
- Hidradenitis Suppurativa and Treatments
- Salivary Gland Disorders and Functions
- T-cell and B-cell Immunology
- NF-κB Signaling Pathways
- Neuroendocrine regulation and behavior
- Cytokine Signaling Pathways and Interactions
- Microscopic Colitis
- Asthma and respiratory diseases
- Complement system in diseases
- Stress Responses and Cortisol
Novartis (Switzerland)
2003-2023
Novartis Institutes for BioMedical Research
2015-2022
CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies CD40 prolong NHPs without events but accompanying B cell depletion, raising the question relative contribution depletion to efficacy anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions antibody can still promote graft survival. The parent...
Genetic and in vivo evidence suggests that aberrant recognition of RNA-containing autoantigens by Toll-like receptors (TLRs) 7 8 drives autoimmune diseases. Here we report on the preclinical characterization MHV370, a selective oral TLR7/8 inhibitor. In vitro, MHV370 inhibits TLR7/8-dependent production cytokines human mouse cells, notably interferon-α, clinically validated driver Moreover, abrogates B cell, plasmacytoid dendritic monocyte, neutrophil responses downstream TLR7/8. vivo,...
<h3>Objective</h3> To examine the role of CD40–CD154 costimulation and effects therapeutic pathway blockade in non-obese diabetic (NOD/ShiLtJ) model Sjögren's syndrome (SS). <h3>Methods</h3> We assessed leucocyte infiltration salivary glands (SGs) from NOD/ShiLtJ mice by immunohistochemistry examined transcriptomics data SG tissue these animals for evidence a CD40 gene signature. Additionally, we dosed MR1 (anti-CD154 antibody) NOD after onset SS-like disease treatment on sialadenitis,...
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in substantial impact on patients' QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify high prevalence IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine...
Abstract CARD-CC complexes involving BCL10 and MALT1 are major cellular signaling hubs. They govern NF-κB activation through their scaffolding properties as well paracaspase function, which cleaves substrates involved in regulation. In human lymphocytes, gain-of-function defects this pathway lead to lymphoproliferative disorders. CARD10, the prototypical protein non-hematopoietic cells, is overexpressed several cancers has been associated with poor prognosis. However, regulation of CARD10...
Psoriasis is a well characterized interleukin (IL)-17A-driven skin disease with neutrophil infiltration and epidermal hyperkeratosis. Several biomarkers, most prominently β-defensin-2 (BD-2), have been identified using local andsystemic invasive measurements as responsive markers of IL-17A-driven pathology. We sought to determinewhether proteins by tape stripping could offer minimally-invasive method assess treatment responses. compared the expression 170 in epidermis (tape stripping) dermis...
<h3>Background</h3> Toll-like receptors (TLR) 7 and 8 are innate sensors of single stranded RNA (ssRNA). Genetic <i>in vivo</i> evidence suggests that aberrant recognition RNA-containing autoantigens by TLR7/8 drives autoimmune diseases (Junt Barchet, 2015). More validation for a pathogenic effect TLR7 in chronic inflammation comes from recent data showing gain-of-function mutation is sufficient to drive lupus-like disease (Brown et al., 2022). <h3>Objectives</h3> Here we report on the...
Abstract Background Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with growing evidence of a critical role the CD40/CD40L pathway (Shenhaji et al Front Immunol 6:529). To confirm and extend these findings, we profiled colonic biopsies from IBD patients active ulcerative colitis (UC) Crohn’s disease (CD) as well non-IBD controls (HV). Methods Mucosal inflamed non-inflamed healthy control subjects were immediately immersed in RNAlater (for RNA) or formaldehyde...