Biology subjects

Rantakari, P.

Publications and source records attributed to Rantakari, P..

7 recordsLinked to original sources

bioRxiv2026

Single-Cell Profiling Reveals Innate Lymphoid Cells and OX40 Activation in Breast Cancer-Related Lymphedema

ABSTRACT Breast cancer-related lymphedema (BCRL) is a severe complication affecting up to 40% of breast cancer survivors. Stage II or chronic disease stages are characterized by upper-limb edema, fibrotic adipose tissue accumulation, pain, and recurrent infections. Despite its clinical burden, BCRL lacks effective pharmacological therapies and the molecular mechanisms driving disease progression remain poorly understood. To better define the regulatory mechanisms underlying chronic BCRL, we performed transcriptomic and quantitative analyses of stromal vascular fraction cells (SVF or non-adipose cell fraction) in BCRL-derived subcutaneous adipose tissue. CD45+ immune cells from stage II BCRL were compared with those from healthy lean and obese adipose tissue controls. Although our analyses identified multiple leukocyte populations, we focused primarily on innate lymphoid cells (ILCs), particularly ILC2 and ILC3 subsets, which were more abundant and active in BCRL tissues. Bioinformatics analysis of cell-cell communication positioned ILCs as central immune-regulatory hubs in BCRL through inflammatory and tissue-remodeling pathways, including connections to IL2, OX40, KIT, and LT signaling. Strong bidirectional communication between ILCs and regulatory T cells via OX40 signaling was uniquely detected in BCRL. Consistent with these findings, protein-based analyses confirmed increased inflammatory mediators and enrichment of the OX40 and OX40L co-stimulatory pair in BCRL tissues. Taken together, our findings identify OX40-dependent ILC-signaling as a novel regulatory program supporting chronic inflammation and pathological tissue remodeling in BCRL.

immunology↗

bioRxiv2025

Tissue-resident neutrophils serve homeostatic and immunological functions in embryos

Development of neutrophils in the bone marrow and their crucial role in first-line defense are well understood in adults, but remarkably little is known about fetal neutrophils. Here, we analyzed the production, distribution, and functions of neutrophils during embryonic development in the mouse. We discovered that multiple non-hematopoietic steady-state organs harbor substantial numbers of immature and mature neutrophils, many of which are localized to tissue parenchyma outside the vessels. Using single-cell transcriptomic analyses, we revealed the presence of neutrophil progenitors and precursor cells in the blood and even in non-hematopoietic tissues in fetal and newborn mice. Embryonic tissue-resident neutrophils were transcriptionally different from embryonic blood-borne neutrophils and adult neutrophils. We demonstrated, through functional analyses, that embryonic neutrophils proliferated actively, had a high glycolytic capacity, and exhibited distinct diurnal rhythmicity. Embryonic neutrophils displayed lineage-specific innate immune effector functions and were responsive to maternal immunostimulation and immunosuppression. Using a genetic embryonic neutrophil depletion model, we discovered that neutrophils impact the piRNA pathway in the testis. Collectively, our data provides an atlas of the fetal neutrophil landscape and dissects their responses in steady-state. SummaryNon-hematopoietic steady-state tissues harbor extravascular immature and mature neutrophils during fetal development. Embryonic neutrophils are endowed with multiple effector mechanisms and also serve homeostatic roles during tissue development.

immunology↗

bioRxiv2025

Embryonic macrophages in brown adipose tissue are spatially associated with developing nerves

Brown adipose tissue (BAT) is a specialized adipose tissue that produces heat through sympathetic nerve-dependent thermogenesis and influences glucose and triglyceride metabolism, making it a potential target for obesity-related diseases. In mice, interscapular BAT (iBAT) emerges on embryonic days (E)14.5-15.5, with extensive vessel and nerve networks still maturing postnatally. These developmental stages are critical for BAT, impacting long-term BAT function. In adult mice, macrophages regulate sympathetic innervation and thermogenesis. However, research on BAT macrophage characters, ontogeny, and functions in early life is lacking. Using single-cell genomics and proteomics, fate-mapping techniques, and 3D imaging, we analyzed iBAT macrophages during early development. We discovered the presence of fetal liver-derived macrophages as early as E15.5, which are later fully replaced by bone marrow-derived macrophages. Transcriptomics data highlight mononuclear phagocyte subpopulations, from which most express macrophage-associated genes (Adgre1, Fcgr1, Csf1r) and monocytic markers (Ccr2, Ly6c2) together. Embryonic macrophages interact closely with developing neural networks, while postnatal bone marrow-derived macrophages associate with blood vessels. Lack of fetal liver-derived macrophages disrupts nerve and vessel development and causes downregulation of genes related to neuronal diseases and protein digestion pathways. Our data suggest that fetal liver-derived macrophages, interacting with BATs developing sympathetic neural network, guide the development of tissue morphology. Understanding further the mechanism behind these events can unravel novel targets for BAT immunomodulation.

immunology↗

bioRxiv2024

Early precursor-derived pituitary gland tissue-resident macrophages play a pivotal role in modulating hormonal balance

The pituitary gland is the central endocrine regulatory organ underneath the brain, producing and releasing a variety of hormones that coordinate major body functions. The physical location of the pituitary gland underneath the brain, though outside the protective blood-brain barrier, leads to a unique immune environment of the pituitary that has not been studied. Here, we defined the development, diversity, spatial niche, and origin of the pituitary gland macrophage subsets using single cell transcriptomics, fate mapping, and imaging. We identified early yolk sac precursors solely seeding pituitary gland macrophages which are maintained by proliferation. Macrophage depletion experiments unveiled the essential contribution of early macrophages in the pituitary glands hormonal production and in modulating the post-pubertal expression of genes related to the sexually dimorphic processes regulated by the pituitary gland. Altogether, these findings provide novel information on pituitary gland macrophages and advance our understanding of immune-endocrine system crosstalk.

immunology↗

bioRxiv2024

Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis

Inflammatory bowel disease (IBD) is a debilitating and relapsing chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly (ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, using a biobank IBD patient cohort as well as two mouse models of colitis, i.e., the IBD-mimicking oral dextran sulfate sodium (DSS) exposure model, and the oral Salmonella exposure model. Parp14 was expressed in the human colon, by cells in the lamina propria, but, in particular, by the epithelial cells with a typical granular staining pattern in the cytosol. The same Parp14 staining pattern was evidenced in both colitis models. Body-wide genetic deficiency of Parp14 in C57BL/6N background sensitized mice to DSS colitis. The Parp14-deficient mice displayed increased rectal bleeding as well as stronger epithelial erosion, Goblet cell loss and immune cell infiltration. The absence of Parp14 did not affect the mouse colon bacterial microbiota based on PacBio long read sequencing. Also, the colon leukocyte populations of Parp14-deficient mice were normal based on flow cytometry. In contrast, we witnessed an altered transcriptional signature in Parp14-deficient mice with bulk tissue RNA-Seq. Gene Ontology (GO)-based classification of differentially expressed genes demonstrated that the colon transcriptional signature of Parp14-deficient mice was dominated by abnormalities in inflammation and infection responses both prior and after the 1-week DSS exposure. Overall, the data indicate that Parp14 has an important role in the maintenance of colon epithelial barrier integrity. The prognostic and predictive biomarker potential of Parp14 in IBD merits further investigation.

immunology↗

bioRxiv2023

Single-cell transcriptome analysis of the early immune response in the lymph nodes of Borrelia burgdorferi-infected mice

Lyme borreliosis is a disease caused by Borrelia burgdorferi sensu lato bacteria. Borrelia burgdorferi is known to induce prolonged extrafollicular immune responses and abnormal germinal center formation. However, the mechanism behind this is poorly understood. The extrafollicular response is characterized by strong plasmablast induction and by an IgM, IgG3, and IgG2b dominant antibody production. These antibodies do not generate a neutralizing type of immunity, and the bacteria eventually establish a persistent infection. Here, we performed single-cell RNA sequencing to characterize the immune landscape of lymph node lymphocytes in the early Borrelia burgdorferi infection in a murine model. Our results indicate that four days after Borrelia burgdorferi infection, a notable B cell proliferation, immunoglobulin class switching to IgG3 and IgG2b isotypes, and plasma cell differentiation are induced, all of which are hallmarks of the extrafollicular immune response. In addition, we found infection-derived upregulation of suppressor of cytokine signalling genes Socs1 and Socs3, and downregulation of genes involved in MHC II antigen presentation in B cells. Our results support the central role of B cells in the immune response of a Borrelia burgdorferi infection, and provide cues of mechanisms behind the determination between extrafollicular and germinal center responses during Borrelia burgdorferi infection.

molecular biology↗

bioRxiv2021

Embigin deficiency leads to delayed embryonic lung development and high neonatal mortality

Embigin (gp70), a transmembrane glycoprotein, has been shown to regulate hematopoietic stem cell and progenitor cell niche. Still, little is known about its expression and function in other organ systems during development or adulthood. By combining immunofluorescence, RNA sequencing, and in vivo mouse models, we show that embigin is highly expressed during development and in adult lung, kidney, epididymis, skin, and testis. Adult Emb-/- mice have a normal lifespan and fertility without apparent pathologies. In contrast, the Emb-/- embryos are significantly smaller than their WT littermates. Markedly increased mortality of the Emb-/- embryos is seen especially during the neonatal period. Embigin is present in the placenta, but placental morphology and gene expression patterns stay unaltered. At E17.5, Emb-/- mice show defective morphogenesis of the lung, low alkaline phosphatase activity in amniotic fluid, and remarkable activation of genes involved in cell proliferation in the lungs. Thus, lung underdevelopment explains the high neonatal mortality. Our work demonstrates the crucial role of embigin during development, and it paves the way to further characterization of embigin in specific organ systems in development and homeostasis. Summary statementEmbigin is a basigin-group transmembrane glycoprotein. In vivo mouse model shows that embigin is crucial for embryonic lung development and neonatal survival.

developmental biology↗