Biology subjects

Kaukonen, D.

Publications and source records attributed to Kaukonen, D..

3 recordsLinked to original sources

bioRxiv2026

Male youth BMI is associated with epigenetic ageing of female descendants but not blood or sperm DNA methylation

Studies based on harvest records indicate that grandparental nutrition in youth is associated with the health traits of grandchildren in a sex-specific lineage. We investigated whether male early adulthood anthropometrics associate with epigenetic age, a measure of general well-being, and DNA methylation, a potential molecular inheritance mechanism, in three generations of descendants. Data on weight, height, BMI and chest circumference measured at military draft examinations (at age 18-24 yrs.) were retrieved from national archives for 1,013 men, herein referred to as Generation Archives (GA). The genome-wide DNA methylation of their descendants participating in the Young Finns Study (YFS) was measured from the blood and sperm from the children (59-80 yrs., nblood = 362, nsperm = 51), grandchildren (34-49 yrs., nblood = 421, nsperm = 98) and great-grandchildren (7-30 yrs., nblood = 200). The men's (GA) BMI had an inverse association with the epigenetic pace of ageing (DunedinPACE) of their daughters ({beta} = -0.01, p = 0.002, n = 169) and the daughters' daughters ({beta} = -0.01, p = 0.049, n = 126) but not with that of their male descendants. From within the YFS cohort, maternal, but not paternal, BMI at ages 13-34 also had an inverse association with the DunedinPACE of the immediate offspring. However, robust evidence for the inheritance mechanism was not found in the analyses between the anthropometric measurements of the GA men and the DNA methylation profiles in the blood and sperm of their descendants.

molecular biology↗

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↗