A5006580364- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- Asthma and respiratory diseases
- Psoriasis: Treatment and Pathogenesis
- Dermatology and Skin Diseases
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Ferroptosis and cancer prognosis
- Renal Diseases and Glomerulopathies
- Cancer Immunotherapy and Biomarkers
- Adipokines, Inflammation, and Metabolic Diseases
- FOXO transcription factor regulation
- Epigenetics and DNA Methylation
- Tissue Engineering and Regenerative Medicine
- Atherosclerosis and Cardiovascular Diseases
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Nanoplatforms for cancer theranostics
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
University Hospital of Basel
2021-2023
University of Basel
2021-2023
Hospital for Special Surgery
2015-2022
Cornell University
2011-2016
Istituto Cantonale di Patologia
2007-2011
Recent studies have shown that the tumor extracellular matrix (ECM) associates with immunosuppression, and targeting ECM can improve immune infiltration responsiveness to immunotherapy. A question remains unresolved is whether directly educates phenotypes seen in tumors. Here, we identify a tumor-associated macrophage (TAM) population associated poor prognosis, interruption of cancer immunity cycle, composition. To investigate was capable generating this TAM phenotype, developed...
Abstract Differences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c + T-bet critical for antiviral disorders. Absence DEF6 SWAP-70, two homologous guanine exchange factors, double-knock-out (DKO) mice leads lupus-like syndrome females marked by accumulation ABCs. Here we demonstrate that DKO ABCs sex-specific differences cell number, upregulation an ISG...
Interactions between sialylated glycans and sialic acid-binding immunoglobulin-like lectin (Siglec) receptors have been recently described as potential new immune checkpoint that can be targeted to improve anticancer immunity. Myeloid cells reported express a wide range of different Siglecs; however, their expression functions on cancer-associated dendritic (DCs) were not fully characterized. We found classical conventional DCs (cDCs) from cancer patient samples high several inhibitory...
Post-transcriptional modifications can control protein abundance, but the extent to which these alterations contribute expression of T helper (TH) lineage-defining factors is unknown. Tight regulation Bcl6 expression, an essential transcription factor for follicular (TFH) cells, critical as aberrant TFH cell expansion associated with autoimmune diseases, such systemic lupus erythematosus (SLE). Here we show that lack SLE risk variant Def6 results in deregulation synthesis cells a result...
Abstract Calcitonin gene–related peptide (CGRP) is a neuropeptide with well-established immunomodulatory functions. CGRP-containing nerves innervate dermal blood vessels and lymph nodes. We examined whether CGRP regulates the outcome of Ag presentation by Langerhans cells (LCs) to T through actions on microvascular endothelial (ECs). Exposure primary murine ECs (pDMECs) followed coculture LCs, responsive CD4+ resulted in increased production IL-6 IL-17A accompanied inhibition IFN-γ, IL-4,...
Germinal center (GC) responses require B cells to respond a dynamic set of intercellular and microenvironmental signals that instruct cell positioning, differentiation, metabolic reprogramming. RHO-associated coiled-coil–containing protein kinase 2 (ROCK2), serine-threonine can be therapeutically targeted by ROCK inhibitors or statins, is key downstream effector RHOA GTPases. Although RHOA-mediated pathways are emerging as critical regulators GC responses, the role ROCK2 in unknown. Here, we...
Epidermal Langerhans cells (LCs) are dendritic APCs that play an important role in cutaneous immune responses. LCs associated with epidermal nerves and the neuropeptides vasoactive intestinal polypeptide (VIP) pituitary adenylate cyclase‐activating (PACAP) inhibit LC Ag presentation for Th1‐type Here, we examined whether PACAP or VIP modulates induction of IL‐17A‐producing CD4 + T cells. Treatment prior to vitro enhanced IL‐17A, IL‐6, IL‐4 production, decreased interferon (IFN)‐γ interleukin...
Introduction: Targeting immune checkpoints with antibodies has significantly improved the outcome of cancer patients, but only few patients have long-term benefits from currently used PD-1/PD-L1 and CTLA-4 inhibitors. New approaches are needed to increase number going into remission after immunotherapy. Glyco-immune new targets for They defined as immune-modulatory pathways including interactions glycans glycan-binding proteins or lectins. The most prominent pathway is sialoglycan-Siglec...
Endothelial cells (ECs) express the nucleotide-binding oligomerization domain (Nod) receptor 2, which recognizes bacterial derivate muramyl dipeptide (MDP). MDP stimulation of these enhances their IL-6 production and may thus contribute to immune inflammatory activities in skin. However, whether ECs are capable influencing development T cell priming its polarization remains unknown. We report that vitro murine bEnd.3 EC line induces, following stimulation, a Th17 at expense Th1 Th2 setting...
Objective Age‐associated/autoimmune B cells (ABCs) are an emerging cell subset with aberrant expansion in systemic lupus erythematosus. ABC generation and differentiation exhibit marked sexual dimorphism, Toll‐like receptor 7 (TLR‐7) engagement is a key contributor to these sex differences. also controlled by interleukin‐21 (IL‐21) its interplay interferon‐γ IL‐4. This study was undertaken investigate whether IL‐13 α1 (IL‐13Rα1), X‐linked that transmits IL‐4/IL‐13 signals, regulates ABCs...
Interferon Regulatory Factors (IRFs) play fundamental roles in dendritic cell (DC) differentiation and function. In particular, IRFs are critical transducers of TLR signaling dysregulation this family factors is associated with the development autoimmune disorders such as Systemic Lupus Erythematosus (SLE). While several expressed DCs their relative contribution to aberrant phenotypic functional characteristics that acquire disease has not been fully delineated. Mice deficient both DEF6...
Abstract Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive subtype of usually associated with inferior outcomes. ABC-DLBCL exhibits plasmablastic features and characterized by aberrancies in the molecular networks controlled IRF4. The signaling pathways that are dysregulated are, however, not fully understood. ROCK2 a serine-threonine kinase whose role lymphomagenesis unknown. Here we show activity constitutively but GCB-DLBCL BL. We furthermore phosphorylates...
Humans lack the enzyme that produces sialic acid N-glycolyl neuraminic (Neu5Gc), but several lines of evidence have shown Neu5Gc can be taken up by mammalian food sources and replace common human N-acetyl (Neu5Ac) in glycans. Cancer tissue has been to increased presence Neu5Gc-containing glycolipids such as ganglioside GM3, which proposed tumor-specific antigens for antibody treatment. Here, we show a previously described against Neu5Gc-GM3 is binding Neu5GC-containing gangliosides strongly...
ABSTRACT Sex differences characterize immune responses to viruses and autoimmune diseases like SLE. ABCs are an emerging population of CD11c + T-bet B cells critical for antiviral disorders. DEF6 SWAP70, two homologous molecules whose combined absence in double-knock-out mice (DKOs) leads a lupus syndrome females marked by accumulation ABCs. Here we demonstrate that DKO exhibit sex-specific their expansion, upregulation ISG signature, further differentiation. BCR sequencing fate mapping...
<h3>Background</h3> A novel subset of B cells termed Age-associated (ABCs) has been recently reported to preferentially accumulate with age in female mice. ABCs are characterised by high expression CD11c and CD11b low levels CD21 CD23. ABC differentiation depends on the transcription factor T-bet is promoted TLR7 stimulation. While have proposed play a key role development autoimmune diseases gender bias observed these disorders molecular mechanisms driving poorly understood. Our laboratory...