A5025050810- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune cells in cancer
- Immune Response and Inflammation
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Phagocytosis and Immune Regulation
- Reproductive System and Pregnancy
- Chemokine receptors and signaling
- Sphingolipid Metabolism and Signaling
- Cholesterol and Lipid Metabolism
- Cancer Immunotherapy and Biomarkers
- Psoriasis: Treatment and Pathogenesis
- IL-33, ST2, and ILC Pathways
Ilya Pharma (Sweden)
2024
Fundación Ciencia and Vida
2013-2021
Karolinska Institutet
2018-2020
Karolinska University Hospital
2020
Science for Life Laboratory
2018
Universidad Andrés Bello
2013-2017
Single-nucleotide polymorphisms in the gene encoding G protein-coupled receptor 35 (GPR35) are associated with increased risk of inflammatory bowel disease. However, mechanisms by which GPR35 modulates intestinal immune homeostasis remain undefined. Here, integrating zebrafish and mouse experimental models, we demonstrate that Gpr35 expression is microbiota dependent enhanced upon inflammation. Moreover, murine GPR35+ colonic macrophages characterized production pro-inflammatory cytokines....
As it has been established that demethylation of lysine 27 histone H3 by the lysine-specific demethylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize inhibition may attenuate autoimmune disorders. We found in vivo administration GSK-J4, a selective inhibitor UTX, ameliorates severity experimental encephalomyelitis (EAE). In vitro experiments revealed anti-inflammatory effect GSK-J4 was exerted through an on dendritic cells (DCs), promoting tolerogenic...
Dendritic cells (DCs) promote T-cell mediated tolerance to self-antigens and induce inflammation innocuous-antigens. This dual potential makes DCs fundamental players in inflammatory disorders. Evidence from colitis mouse models bowel diseases (IBD) patients indicated that gut IBD is driven mainly by T-helper-1 (Th1) Th17 cells, suggesting an essential role for the development of IBD. Here we show GSK-J4, a selective inhibitor histone demethylase JMJD3/UTX, attenuated reducing increasing...
Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play crucial role in the maintenance self-tolerance. They can be generated thymus as well periphery through differentiation naïve CD4 + cells. The forkhead box P3 transcription factor (Foxp3) is molecule regulating generation function Tregs. Here we show foxp3 gene promoter becomes hyperacetylated vitro differentiated Tregs compared to We also histone deacetylase inhibitor TSA stimulated into this...
Treatments of colitis, inflammation the intestine, rely on induction immune suppression associated with systemic adverse events, including recurrent infections. This treatment strategy is specifically problematic in increasing population patients cancer checkpoint inhibitor (ICI)-induced as also interferes ICI-treatment response. Thus, there a need for local-acting treatments that reduce and enhance intestinal healing. Here, we investigated effect safety bacterial delivery short-lived...
The gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, is a major driver of intestinal CD4+ T helper (Th) cell differentiation. Dietary can be sensed nuclear receptors (NRs) that consequently exert pleiotropic effects including immune modulation. Here, we found under homeostatic conditions NR Liver X receptor (LXR), sensor cholesterol metabolites, regulates RORγt+ CD4 cells in intestine draining mesenteric lymph node (MLN). While LXR activation led...
The gut homing receptor integrin α4β7 is essential for the migration of pro-inflammatory T cells into mucosa. Since intestinal neoplasia has been associated with chronic inflammation, we investigated whether interfering gut-homing affects tumorigenesis. Using chemically induced and spontaneous tumor models showed that lack β7 significantly impairs growth without affecting frequencies, a mild translatable effect on overall survival. This correlates human data showing lower MAdCAM-1 expression...
Abstract JMJD3 a demethylase of lysine 27 histone H3 (H3K27) plays an important role in immune cells and inflammatory responses, thus appears as attractive target for the treatment diseases. Recently, GSK-J4, selective potent inhibitor was synthesized. We previously showed that GSK-J4 induced tolerogenic phenotype on dendritic (DCs) promoting generation stability Tregs well enhancing their suppressive function. However, underlying mechanisms remain unclear. Because acts upon DCs, we...
Abstract The gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, is a major driver of intestinal CD4 + T helper (Th) cell differentiation. Dietary can be sensed nuclear receptors (NRs) that consequently exerts pleiotropic effects including immune modulation. However, how NRs regulate distinct Th subsets remain poorly understood. Here, we found under homeostatic condition Liver X receptor (LXR), sensor cholesterol metabolites, controls RORγt Treg Th17...