A5091230903- Immune cells in cancer
- Caveolin-1 and cellular processes
- Clusterin in disease pathology
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Neonatal Respiratory Health Research
- Lymphatic System and Diseases
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- Hormonal Regulation and Hypertension
- Cell Adhesion Molecules Research
- Heat shock proteins research
- Erythrocyte Function and Pathophysiology
- Galectins and Cancer Biology
- Microbial metabolism and enzyme function
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Adenosine and Purinergic Signaling
- Bone and Dental Protein Studies
- Estrogen and related hormone effects
- Neuroscience of respiration and sleep
- T-cell and B-cell Immunology
- Medicinal Plant Pharmacodynamics Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Lipid metabolism and disorders
- Kruppel-like factors research
University of Turku
2016-2025
Åbo Akademi University
2020-2025
Turku Centre for Computer Science
2020-2025
Zero to Three
2020
Finnish Institute for Health and Welfare
2013
University of Helsinki
2010
Nonalcoholic fatty liver disease (NAFLD) encompasses a range of manifestations, including steatosis and cirrhosis. Progressive is characterized by hepatic leukocyte accumulation in the form steatohepatitis. The adhesion molecule vascular protein-1 (VAP-1) membrane-bound amine oxidase that promotes recruitment to liver, soluble (sVAP-1) accounts for most circulating monoamine activity, has insulin-like effects, can initiate oxidative stress. Here, we determined VAP-1 expression increased...
<h3>Objective</h3> <i>miR-21</i> is an oncomir highly upregulated in hepatocellular carcinoma and early stages of liver diseases characterised by the presence steatosis. Whether upregulation contributes to hepatic metabolic disorders their progression towards cancer unknown. This study aims at investigating role <i>miR-21/miR-21*</i> associated with diet-induced obesity (DIO). <h3>Design</h3> Constitutive knockout (miR21KO) liver-specific (LImiR21KO) mice were generated. Mice then fed...
Significance Organ fibrosis is a major cause of global morbidity and mortality. It driven by chronic inflammation associated oxidative stress with depletion cellular antioxidant defenses. We demonstrate pathway in which the evolutionarily conserved receptor stabilin-1 on tissue-infiltrating macrophages provides second-line defense to prevent tissue damage from stress. Stabilin-1 + monocytes take up malondialdehyde-LDL (MDA-LDL), product lipid peroxidation, form ceroid-laden macrophages....
Macrophages serve multiple functions including immune regulation, morphogenesis, tissue homeostasis and healing reactions. The current paradigm holds that mammary gland macrophages first arise postnatally during the prepubertal period from bone marrow-derived monocytes. Here we delineate origins of tissue-resident using high-dimension phenotypic analyses, cell-fate mapping experiments, gene-deficient mice lacking selective macrophage subtypes, antibody-based depletion strategies. We show are...
Abstract In the testis, interstitial macrophages are thought to be derived from yolk sac during fetal development, and later replaced by bone marrow-derived macrophages. By contrast, peritubular have been reported emerge first in postnatal testis solely represent descendants of monocytes. Here, we define new monocyte macrophage types using high-dimensional single-cell analyses. Our results show that a dominant contribution liver-derived precursors, while generated already at birth embryonic...
Abstract Purpose: Immunosuppressive leukocytes and vasculature are important host cell components regulating tumor progression. Clever-1/Stabilin-1, a multifunctional scavenger adhesion receptor, is constitutively present on subset of type II macrophages lymphatic endothelium, but its functional role in cancer unknown. Experimental Design: Here, we generated full Clever-1 knockout mice cell-specific ones lacking either or endothelium. We also used anti-Clever-1 antibody therapy to treat B16...
Lymph nodes (LNs) filter lymph to mount effective immune responses. Small soluble lymph-borne molecules from the periphery enter draining LNs via a reticular conduit system. Intact antibodies and other larger molecules, in contrast, are physically unable conduits, they thought be transported only within migratory DCs after proteolytic degradation. Here, we discovered that large biomolecules seconds into parenchyma of LN an intact form. Mechanistically, found uptake is receptor-independent,...
Despite the ubiquitous function of macrophages across body, diversity, origin, and adrenal gland remain largely unknown. We define heterogeneity immune cells using single-cell RNA sequencing use genetic models to explore developmental mechanisms yielding macrophage diversity. populations monocyte-derived embryonically seeded identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates maintenance in female...
SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role SHARPIN in lymphocyte adhesion, polarization, and found that localizes to trailing edges (uropods) both mouse human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1), which is one major endothelial ligands for leukocytes. cells adhere better ICAM-1 show highly elongated tails when migrating. The increased...
Insulin-like growth factor 2 (IGF2), produced and secreted by adult β-cells, functions as an autocrine activator of the β-cell insulin-like 1 receptor signaling pathway. Whether this activity IGF2 plays a physiological role in whole-body physiology is not known. Here, we studied mice with β-cell–specific inactivation Igf2 (βIGF2KO mice) assessed mass function aging, pregnancy, acute induction insulin resistance. We showed that glucose-stimulated secretion (GSIS) was markedly reduced old...
Adipose tissue macrophages (ATMs) regulate homeostasis and contribute to the metabolically harmful chronic inflammation in obese individuals. While evident heterogeneity of resident ATMs has been described previously, their phenotype, developmental origin, functionality remain inconsistent. We analyzed white adipose (WAT) during diet interventions using comprehensive unbiased single-cell mass cytometry genetic lineage tracking models. now provide a uniform definition individual subsets ATMs....
Hydroxysteroid (17β) dehydrogenases (HSD17Bs) have a significant role in steroid metabolism by catalyzing the conversion between 17-keto and 17β-hydroxysteroids. However, several studies vitro shown that some of these enzymes may also be involved other metabolic pathways. Among enzymes, HSD17B12 has been to both biosynthesis estradiol elongation essential very long fatty acids vivo. To investigate function mammalian vivo, we generated mice with null mutation Hsd17b12 gene (HSD17B12KO mice)...
Macrophage mannose receptor (MRC) is one of the few molecules known to be involved in lymphocyte trafficking via lymphatic vessels. In endothelial cells efferent lymphatics, it binds L-selectin on lymphocytes. afferent MRC mediates both normal and malignant L-selectin-negative draining lymph nodes.This work was designed search for additional ligands elucidate how lymphocytes migrate into nodes.Using immunoprecipitation binding studies with natural recombinant proteins, we show that CD44 can...
Mutations of the PALB2 tumor suppressor gene in humans are associated with hereditary predisposition to breast and also some other cancers.In present study, we have characterized mice deficient Palb2.The data show that Palb2 (1/2) normal fertile, lack macroscopic tumors when followed up till age 8 months.Homozygous (HO) (2/2) embryonic lethality die at E9.5 latest.The mutant embryos smaller size, developmentally retarded display defective mesoderm differentiation after gastrulation.In...
Hydroxysteroid (17β) dehydrogenase 7 (HSD17B7) has been shown to catalyze the conversion of both estrone estradiol (17-ketosteroid reductase activity) and zymosterone zymosterol (3-ketosteroid activity involved in cholesterol biosynthesis) vitro. To define metabolic role enzyme vivo, we generated knockout mice deficient (HSD17B7KO). The data showed that lack HSD17B7 results a blockage de novo biosynthesis mouse embryos HSD17BKO die at embryonic day (E) 10.5. Analysis neural structures...
Significance This paper elucidates one of the enigmas in immunology: What determines discriminative traffic via afferent and efferent lymphatics? We report so far unrecognized vastly distinct molecular profiles lymphatic endothelial cells (LECs) arms system lymph nodes. Moreover, work takes three hit molecules to more detailed analyses regarding their expression function, presents a previously unknown function regulation lymphocyte for macrophage scavenger receptor on LECs subcapsular sinus....
Abstract Endothelial cells contain several nanoscale domains such as caveolae, fenestrations and transendothelial channels, which regulate signaling permeability. These structures can be covered by filter-like diaphragms. A transmembrane PLVAP (plasmalemma vesicle associated protein) protein has been shown to necessary for the formation of The expression, subcellular localization fenestra-forming role in liver sinusoidal endothelial (LSEC) have remained controversial. Here we show that LSEC...
miR-22 is one of the most abundant miRNAs in liver and alterations its hepatic expression have been associated with development steatosis insulin resistance, as well cancer. However, pathophysiological roles miR-22-3p deregulated metabolism obesity cancer remains poorly characterized. Herein, we observed that non-alcoholic fatty disease (NAFLD) context are not consistent various human cohorts animal models contrast to well-characterized downregulation cancers. To unravel role...
Brown adipose tissue (BAT) is a specialized that produces heat through sympathetic nerve-dependent thermogenesis and influences glucose triglyceride metabolism, making it potential target for obesity-related diseases. In mice, interscapular BAT (iBAT) emerges on embryonic days (E)14.5-15.5, with extensive vessel nerve networks still maturing postnatally. These developmental stages are critical BAT, impacting long-term function. adult macrophages regulate innervation thermogenesis. However,...
CD73/ecto-5'-nucleotidase is a key enzyme in the regulation of purinergic signaling and inflammatory reactions. It hydrolyzes extracellular AMP into adenosine, which dampens immune cell activation, reduces leukocyte trafficking. By comparing CD73 expression function mononuclear endothelial cells (ECs) blood lymph, we show that purines activity have differential effects these two vascular systems. We found CD8-positive T lymphocytes CD19-positive B human lymph expressed high levels other...
Abstract Macrophages, which are highly diverse in different tissues, play a complex and vital role tissue development, homeostasis, inflammation. The origin heterogeneity of tissue‐resident monocytes macrophages ovaries remains unknown. Here we identify three monocyte populations five macrophage the adult using high‐dimensional single cell mass cytometry. Ontogenic analyses fate mapping models depletion experiments revealed infiltration by both yolk sac fetal liver‐derived already during...