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Deciphering the regulation of tissue adaptation of regulatory T cells
No full text© 2025 Darya MalkoRegulatory T (Treg) cells are specialized immune cells of the T cell lineage that are indispensable for the maintenance of immune homeostasis and prevention of immune mediated pathology. Most Treg cells develop in the thymus and undergo a distinct differentiation program in the periphery that is essential to acquire a fully suppressive effector phenotype. This process endows Treg cells with the ability to migrate to multiple non-lymphoid tissues where they further mature and acquire tissue specific features. Notably, these tissue-resident Treg cells perform multiple non-immune functions including the maintenance of tissue integrity and repair, as well as the regulation of systemic metabolism. In this study, we further elucidated the molecular control of tissue-specific effector Treg cell adaptation, focusing on two non-lymphoid tissues: the central nervous system and the adipose tissue.
The central nervous system (CNS), comprised of the brain and spinal cord, is responsible for the reception, processing, and reaction to sensory stimuli. Recent insights have unveiled the presence of immune cells in the CNS, among which Treg cells have been shown to promote tissue homeostasis at steady state and during pathology, such as in patients that experienced ischemic stroke. However, the role of Treg cells in neurodegenerative diseases remain poorly understood. Multiple Sclerosis is an incurable chronic autoimmune disease of the CNS with a multifactorial origin and high pathological heterogeneity. In this study, we employed a mouse model of experimental autoimmune encephalomyelitis, that recapitulates human Multiple Sclerosis, to investigate the impact of hypoxia-inducible factor 1-alpha (Hif1α) on Treg cells during disease progression. Hif1α, a transcription factor induced by hypoxia and inflammation, is elevated in Multiple Sclerosis patients and furthermore has been shown to attenuate Treg cell development and function. Our findings indicate that Treg cells harboring a Hif1α deletion switch to mitochondrial respiration at the inflammation side, possibly enhancing their effector function, and finally ameliorating disease progression.
The visceral adipose tissue (VAT) is an endocrine organ that is essential for metabolic homeostasis and energy storage. Despite these physiological functions, excessive white adipose tissue accumulation in response to age or diet promotes tissue inflammation, increasing the risk of developing metabolic morbidities such as type 2 diabetes. Thus, in particular when considering the global rise of obesity, it becomes crucial to better understand the interplay between the immune system and the VAT. Treg cells are critical for dampening the inflammation in the VAT, preserving tissue homeostasis and systemic metabolism. Our labs and others have shown that under steady state conditions, Treg cells are enriched in the VAT, where they heterogeneous and accumulate in a sex dependent manner. Two main VAT Treg cell clusters can be described based on their expression of the interleukin-33 receptor ST2 and the chemokine receptor CXCR3. The prototypical ST2+ Treg cells highly dominate the VAT of male animals and differentiate in dependency of the transcription factors peroxisome proliferator-activated receptor-γ and Gata3; whereas CXCR3+ Treg cells rely on the transcription factor T-bet and are enriched in female mice. Alongside distinct phenotypical and functional characteristics, this study uncovered differences in the metabolic requirements of these Treg cell populations showing elevated usage of the amino acid metabolism in ST2+ Treg cells, while CXCR3+ Treg cells utilized mitochondrial respiration to maintain their high proliferative capacity.
This study further utilized novel transgenic mouse models, dietary conditions, and in vitro assays to investigate the VAT microenvironmental signals that shape Treg cell differentiation, heterogeneity, and function. Our results thereby identified a pivotal role for the transforming growth factor-beta (TGF-β) in maintaining VAT Treg cell homeostasis. Ablation of the TGF-β signaling in Treg cells favored the expansion of CXCR3+ VAT Treg cells, while reducing their overall sensitivity to interleukin-33 by the loss of ST2 expression. Phenotypic and functional changes in Treg cells in turn reshaped the VAT’s cell composition, creating an anti-inflammatory environment that prevented fat accumulation, even when mice were fed a high fat diet. Together, these results illuminate a novel pathway by which TGF-β underpins VAT Treg cell differentiation and function, contributing to the maintenance of VAT immune homeostasis and tissue morphology, and may constitute a new therapeutic target in metabolic disease
Deciphering the regulation of tissue adaptation of regulatory T cells
No full textRegulatory T (Treg) cells are specialised immune cells of the CD4+ T cell lineage that are indispensable for the maintenance of immune homeostasis and prevention of immune-mediated pathology. Most Treg cells develop in the thymus and undergo a distinct differentiation program in the periphery, which is essential for the acquisition of a fully suppressive effector phenotype. This process endows Treg cells with the ability to migrate to multiple non-lymphoid tissues, where they mature and acquire tissue-specific features. Notably, tissue-resident Treg cells perform multiple non-immune functions, including the maintenance of tissue integrity and repair, as well as the regulation of systemic metabolism. In this study, we investigated the molecular control of tissue-specific effector Treg cell adaptation, focusing on two non-lymphoid tissues, the central nervous system (CNS) and adipose tissue. The CNS, composed of the brain and spinal cord, is responsible for reception, processing, and reaction to sensory stimuli. Recent studies have revealed the presence of immune cells, including Treg cells, in the CNS. However, the role of Treg cells in chronic CNS diseases, such as Multiple Sclerosis, remains poorly understood. In this study, we employed a mouse model of experimental autoimmune encephalomyelitis, recapitulating human Multiple Sclerosis, to investigate the effects of hypoxia-inducible factor 1-alpha (Hif1a) on Treg cells during disease progression. Hif1a, a transcription factor induced by hypoxia and inflammation, is elevated in Multiple Sclerosis patients. Independently, it has been shown to attenuate Treg cell development and function. My findings indicate that Treg cells that lack Hif1a switch to mitochondrial respiration at sites of inflammation. This change may enhance their effector function, which could have contributed to the alleviation of disease progression in female mice. Visceral adipose tissue (VAT) functions as an endocrine organ vital for metabolic homeostasis and energy storage. However, excessive accumulation of white adipose tissue due to aging or diet triggers tissue inflammation, increasing the risk of metabolic disorders, such as type 2 diabetes. Given the global obesity rise, understanding the interaction of the immune system with VAT is essential. Treg cells are critical for dampening VAT inflammation preserving tissue homeostasis and systemic metabolism. Research, including our own, indicates that a heterogeneous population of Treg cells accumulates in the VAT in a sex-dependent manner under steady-state conditions. These Treg cells can be categorised into two main clusters based on their expression of the interleukin (IL)-33 receptor ST2 and the chemokine receptor CXCR3. In male animals, prototypical ST2+ Treg cells, which depend on the transcription factors PPAR? and GATA3, are predominant. Conversely, CXCR3+ Treg cells, which rely on the transcription factor T-bet, are enriched in female mice. In addition to distinct phenotypical and functional characteristics, this study revealed differences in the metabolic requirements of these Treg cell populations showing elevated usage of amino acid metabolism in ST2+ Treg cells, while CXCR3+ Treg cells utilised mitochondrial respiration to maintain their high proliferative capacity. Furthermore, this study utilised novel transgenic mouse models, dietary conditions, and in vitro assays to investigate VAT microenvironmental signals that shape Treg cell differentiation, heterogeneity, and function. Our results identified a pivotal role for transforming growth factor-beta (TGF-ß) in maintaining VAT Treg cell homeostasis. Ablation of TGF-ß signalling in Treg cells favoured the expansion of CXCR3+ VAT Treg cells while reducing their overall sensitivity to IL-33 by the loss of ST2 expression. Phenotypic and functional changes in Treg cells in turn reshaped the cellular composition of VAT, creating an anti-inflammatory environment that prevented fat accumulation, even under high fat diet. Together, these results highlight a novel pathway by which TGF-ß steers VAT Treg cell differentiation and function, thereby contributing to the maintenance of VAT immune homeostasis and tissue morphology. Therefore, manipulation of Treg cells via TGF-ß may constitute a new, promising therapeutic target for metabolic diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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