A5036524441- Inflammatory Bowel Disease
- IL-33, ST2, and ILC Pathways
- Microscopic Colitis
- Immune Cell Function and Interaction
- Helicobacter pylori-related gastroenterology studies
- Immunodeficiency and Autoimmune Disorders
- Eosinophilic Esophagitis
- Celiac Disease Research and Management
- Lymphoma Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- Dermatology and Skin Diseases
- T-cell and B-cell Immunology
- Parasites and Host Interactions
- Autoimmune and Inflammatory Disorders
- Acute Lymphoblastic Leukemia research
- Tuberculosis Research and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Long-Term Effects of COVID-19
- Cancer-related molecular mechanisms research
- Viral-associated cancers and disorders
- Mycobacterium research and diagnosis
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Whipple's Disease and Interleukins
- Systemic Lupus Erythematosus Research
Johnson & Johnson (United States)
2019-2024
Janssen (Belgium)
2024
Janssen (United States)
2013-2022
University of Pennsylvania
2007-2015
In-Q-Tel
2008
University of Wisconsin–Madison
2002
Alterations in the composition of intestinal commensal bacteria are associated with enhanced susceptibility to multiple inflammatory diseases, including those conditions interleukin (IL)-17–producing CD4+ T helper (Th17) cells. However, relationship between and expression proinflammatory cytokines remains unclear. Using germ-free mice, we show that frequency Th17 cells large intestine is significantly elevated absence bacteria. Commensal-dependent IL-17 family member IL-25 (IL-17E) by...
Differentiation and recruitment of alternatively activated macrophages (AAMacs) are hallmarks several inflammatory conditions associated with infection, allergy, diabetes, cancer. AAMacs defined by the expression Arginase 1, chitinase-like molecules, resistin-like molecule (RELM) α/FIZZ1; however, influence these molecules on development, progression, or resolution diseases is unknown. We describe generation RELM-α–deficient (Retnla−/−) mice use a model T helper type 2 (Th2)...
Tissue homeostasis is perturbed in a diversity of inflammatory pathologies. These changes can elicit endoplasmic reticulum (ER) stress, protein misfolding, and cell death. ER stress triggers the unfolded response (UPR), which promote recovery proteostasis survival or trigger programmed Here, we leveraged single-cell RNA sequencing to define dynamic transcriptional states associated with adaptive versus terminal UPR mouse intestinal epithelium. We integrated these programs genome-scale CRISPR...
Objective IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures disease may augment current endpoints including the potential for less invasive assessments. Design Transcriptome analysis on 712 endoscopically defined inflamed (Inf) 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn’s disease, n=421 UC 243 controls) in Mount Sinai Colitis Registry were used identify genes differentially expressed between Inf Non-Inf generate a molecular...
SERPINE1/PAI-1 is elevated in the colon tissue of most difficult-to-treat patients with IBD and leads to worsening experimental colitis.
Interleukin (IL) 31Rα (glycoprotein 130–like monocyte receptor and glycoprotein receptor) heterodimerizes with oncostatin M β to bind IL-31, a cytokine expressed preferentially by CD4+ T helper type 2 (Th2) cells. However, the functions of IL-31–IL-31R signaling in immune regulation remain unknown. Here, we identify novel role for IL-31R limiting inflammation lung. After intravenous injection Schistosoma mansoni eggs, IL-31Rα−/− mice developed severe pulmonary inflammation, characterized an...
The transcription factor T-bet has been most prominently linked to NK and T cell production of IFN-γ, a cytokine required for the control diverse array intracellular pathogens. Indeed, in mice challenged with parasite Toxoplasma gondii, responses are characterized by marked increases expression. Unexpectedly, T-bet(-/-) infected T. gondii develop strong IFN-γ response that controls replication at challenge site, but display high burdens secondary sites colonized succumb infection. loss had...
Genome-wide association studies (GWAS) have identified loci reproducibly associated with inflammatory bowel disease (IBD) and other immune-mediated diseases; however, the molecular mechanisms underlying most of genetic susceptibility remain undefined. Expressional quantitative trait (eQTL) disease-relevant tissue can be employed in order to elucidate genes pathways affected by disease-specific variance.In this study, we derived eQTLs for human whole blood intestine tissues anti-tumor...
ABSTRACT Epstein-Barr virus (EBV) is a human herpesvirus capable of establishing latent state in B lymphocytes. The product the immediate-early BZLF1 gene, Zta, transcriptional transactivator essential for viral DNA amplification and virion production. Previously, we identified negative cis -acting element within promoter termed ZV. ZV contains sequence 5′-CAGGTA-3′ located at nucleotides −17 to −12 relative transcription initiation site. It specifically binds cellular factor, ZVR. Based on...
Abstract Multiple conflicting findings have been presented which indicate that EBV may be found in anywhere from 0% to 51% of breast carcinomas. When has causally associated with other human cancers, its DNA and one or more viral products detected most tumor cells a given biopsy. To test whether such an association cancer, we measured the number molecules per cell matched normal biopsies 45 patients using real-time quantitative PCR. In no case could consistently detected, either two...
Abstract IL-31 is a recently identified cytokine made predominantly by CD4+ Th2 cells and its receptor, IL-31R, expressed number of cell types including monocytes, epithelial cells, T cells. Originally as potential mediator inflammation in the skin, we reported novel function for endogenous IL-31R interactions limiting type 2 lung. However, whether IL-31-IL-31R regulate immunity or at other mucosal sites, such gut, unknown. In this study, report regulatory role intestine following infection...
BackgroundInflammatory bowel disease (IBD) is a complex with variable presentation, progression, and response to therapies. Current classification based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, thus we measured 39 circulating immune cell types in large cohort of IBD control subjects performed immunotype:phenotype associations.MethodsWe fluorescence-activated sorting or CyTOF analysis from 728 Crohn's disease, 464 ulcerative...
The role of long noncoding RNAs (lncRNAs) in disease is incompletely understood, but their regulation inflammation increasingly appreciated. We addressed the extent lncRNA involvement inflammatory bowel (IBD) using biopsy-derived RNA-sequencing data from a large cohort deeply phenotyped patients with IBD. Weighted gene correlation network analysis revealed modules lncRNAs coexpressed protein-coding genes enriched for biological pathways, correlated epithelial and immune cell signatures, or...
Abstract Immune dysregulation and cytokine release syndrome have emerged as pathological hallmarks of severe Coronavirus Disease 2019 (COVID-19), leading to the evaluation antagonists therapeutic agents. A number immune-directed therapies being considered for COVID-19 patients are already in clinical use chronic inflammatory conditions like bowel disease (IBD). These considerations led us systematically examine intersections between GI tract during health intestinal inflammation. We observed...
The intestinal mucosa is the largest body surface exposed to environment. While there are common features when comparing immune responses along mucosa, small bowel and colon exhibit striking differences in their mechanisms driving regulation. vitamin A (VA) metabolite all-trans retinoic acid (RA) signaling via RA nuclear receptors plays a key role homeostasis bowel, recent work indicates that required for establishing tolerance dietary antigens upper tract by inducing α4β7+CCR9+ gut-tropic...
Therapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn's disease (CD) patients, we examined the predictive value an epithelial cell biomarker, ileal microvillar length (MVL), clinical response to ustekinumab (UST) and vedolizumab (VDZ) its relationship another intestinal (IEC) pyroptosis, with respect VDZ.Ileal biopsies from UNITI-2 randomized controlled trial were analyzed MVL as a predictor UST. 5-center academic retrospective cohort CD was determine VDZ....