ArticleMolecular metabolism2019
Short-term cold exposure supports human Treg induction in vivo.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Effects of a short-term cold exposure on circulating microRNAs and metabolic parameters in healthy adult subjects.Journal of cellular and molecular medicine · 2022Trial
- Cold exposure and metabolic health: Therapeutic potential for obesity, diabetes, and beyond.Physiological reports · 2026Review
- Regulatory T cells in the mouse hypothalamus control immune activation and ameliorate metabolic impairments in high-calorie environments.Nature communications · 2025Article
- Metabolic and stress response adaptations in T cells to fever and physiological heat.Trends in immunology · 2025Review
- Immune Regulatory Crosstalk in Adipose Tissue Thermogenesis.Comprehensive Physiology · 2025Review
- Regulatory T cells require IL6 receptor alpha signaling to control skeletal muscle function and regeneration.Cell metabolism · 2023Article
- Immune cell cholinergic signaling in adipose thermoregulation and immunometabolism.Trends in immunology · 2022Review
- Immune Cells in Thermogenic Adipose Depots: The Essential but Complex Relationship.Frontiers in endocrinology · 2022Review
- Effect of BMI on the Thermogenic Response to Cold Exposure and Associated Changes in Metabolism and Browning Markers in Adult Humans.Obesity facts · 2022Article
- Tissue Resident Foxp3Frontiers in immunology · 2022Review
- MECHANISMS IN ENDOCRINOLOGY: Human brown adipose tissue as a therapeutic target: warming up or cooling down?European journal of endocrinology · 2021Review
- Brown Fat-Activating Lipokine 12,13-diHOME in Human Milk Is Associated With Infant Adiposity.The Journal of clinical endocrinology and metabolism · 2021Article
- Advances in Human Immune System Mouse Models for Personalized Treg-Based Immunotherapies.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveObesity and type-2 diabetes (T2D) are metabolic diseases that represent a critical health problem worldwide. Metabolic disease is differentially associated with fat distribution, while visceral white adipose tissue (VAT) is particularly prone to obesity-associated inflammation. Next to their canonical function of immune suppression, regulatory T cells (Tregs) are key in controlling adipose tissue homeostasis. Towards understanding the molecular underpinnings of metabolic disease, we focus on how environmental-metabolic stimuli impinge on the functional interplay between Tregs and adipose tissue. Here, cold exposure or beta3-adrenergic signaling are a promising tool to increase energy expenditure by activating brown adipose tissue, as well as by reducing local inflammation within fat depots by supporting immunosuppressive Tregs. However, in humans, the underlying mechanisms that enable the environmental-immune crosstalk in the periphery and in the respective tissue remain currently unknown.
methodsWe used combinatorial approaches of next generation humanized mouse models and in vitro and in vivo experiments together with beta3-adrenergic stimulation to dissect the underlying mechanisms of human Treg induction exposed to environmental stimuli such as cold. To test the translational relevance of our findings, we analyzed samples from the FREECE study in which human subjects were exposed to individualized cooling protocols. Samples were analyzed ex vivo and after in vitro Treg induction using qRT-PCR, immunofluorescence, as well as with multicolor flow cytometry and cell sorting.
resultsIn vivo application of the beta3-adrenergic receptor agonist mirabegron in humanized mice induced thermogenesis and improved the Treg induction capacity of naïve T cells isolated from these animals. Using samples from the human FREECE study, we demonstrate that a short-term cold stimulus supports human Treg induction in vitro and in vivo. Mechanistically, we identify BORCS6 encoding the Ragulator-interacting protein C17orf59 to be significantly induced in human CD4
conclusionsThese novel insights into the molecular underpinnings of human Treg induction suggest an important role of Tregs in linking environmental stimuli with adipose tissue function and metabolic diseases. Moreover, these discoveries shed new light on potential approaches towards tailored anti-inflammatory concepts that support human adipose tissue homeostasis by enabling Tregs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.