Interferon gamma constrains type 2 lymphocyte niche boundaries during mixed inflammation.

Allergic immunity is orchestrated by group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells prominently arrayed at epithelial- and microbial-rich barriers. However, ILC2s and Th2 cells are also present in fibroblast-rich niches within the adventitial layer of larger vessels and similar boundary structures in sterile deep tissues, and it remains unclear whether they undergo dynamic repositioning during immune perturbations. Here, we used thick-section quantitative imaging to show that allergic inflammation drives invasion of lung and liver non-adventitial parenchyma by ILC2s and Th2 cells. However, during concurrent type 1 and type 2 mixed inflammation, IFNγ from broadly distributed type 1 lymphocytes directly blocked both ILC2 parenchymal trafficking and subsequent cell survival. ILC2 and Th2 cell confinement to adventitia limited mortality by the type 1 pathogen Listeria monocytogenes. Our results suggest that the topography of tissue lymphocyte subsets is tightly regulated to promote appropriately timed and balanced immunity.

Spatial maps of T cell receptors and transcriptomes reveal distinct immune niches and interactions in the adaptive immune response.

T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their clonotypic T cell receptors (TCRs). Determining the spatial distributions of T cell clonotypes in tissues is essential to understanding T cell behavior, but spatial sequencing methods remain unable to profile the TCR repertoire. Here, we developed Slide-TCR-seq, a 10-µm-resolution method, to sequence whole transcriptomes and TCRs within intact tissues. We confirmed the ability of Slide-TCR-seq to map the characteristic locations of T cells and their receptors in mouse spleen. In human lymphoid germinal centers, we identified spatially distinct TCR repertoires. Profiling T cells in renal cell carcinoma and melanoma specimens revealed heterogeneous immune responses: T cell states and infiltration differed intra- and inter-clonally, and adjacent tumor and immune cells exhibited distinct gene expression. Altogether, our method yields insights into the spatial relationships between clonality, neighboring cell types, and gene expression that drive T cell responses.

Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.

Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were most intimately associated with adventitial stromal cells (ASCs), a mesenchymal fibroblast-like subset that expresses interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP). In vitro, ASCs produced TSLP that supported ILC2 accumulation and activation. ILC2s and IL-13 drove reciprocal ASC expansion and IL-33 expression. During helminth infection, ASC depletion impaired lung ILC2 and Th2 cell accumulation and function, which are in part dependent on ASC-derived IL-33. These data indicate that adventitial niches are conserved sites where ASCs regulate type 2 lymphocyte expansion and function.

Heterotypic interaction promotes asymmetric division of human hematopoietic progenitors.

Hematopoietic stem and progenitor cells (HSPCs) give rise to all cell types of the hematopoietic system through various processes, including asymmetric divisions. However, the contribution of stromal cells of the hematopoietic niches in the control of HSPC asymmetric divisions remains unknown. Using polyacrylamide microwells as minimalist niches, we show that specific heterotypic interactions with osteoblast and endothelial cells promote asymmetric divisions of human HSPCs. Upon interaction, HSPCs polarize in interphase with the centrosome, the Golgi apparatus, and lysosomes positioned close to the site of contact. Subsequently, during mitosis, HSPCs orient their spindle perpendicular to the plane of contact. This division mode gives rise to siblings with unequal amounts of lysosomes and of the differentiation marker CD34. Such asymmetric inheritance generates heterogeneity in the progeny, which is likely to contribute to the plasticity of the early steps of hematopoiesis.

A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System.

Immune cells communicate by exchanging cytokines to achieve a context-appropriate response, but the distances over which such communication happens are not known. Here, we used theoretical considerations and experimental models of immune responses in vitro and in vivo to quantify the spatial extent of cytokine communications in dense tissues. We established that competition between cytokine diffusion and consumption generated spatial niches of high cytokine concentrations with sharp boundaries. The size of these self-assembled niches scaled with the density of cytokine-consuming cells, a parameter that gets tuned during immune responses. In vivo, we measured interactions on length scales of 80-120 µm, which resulted in a high degree of cell-to-cell variance in cytokine exposure. Such heterogeneous distributions of cytokines were a source of non-genetic cell-to-cell variability that is often overlooked in single-cell studies. Our findings thus provide a basis for understanding variability in the patterning of immune responses by diffusible factors.

Visualization and functional characterization of lymphoid organ fibroblasts.

Fibroblastic reticular cells (FRCs) are specialized stromal cells of lymphoid organs that generate the structural foundation of the tissue and actively interact with immune cells. Distinct FRC subsets position lymphocytes and myeloid cells in specialized niches where they present processed or native antigen and provide essential growth factors and cytokines for immune cell activation and differentiation. Niche-specific functions of FRC subpopulations have been defined using genetic targeting, high-dimensional transcriptomic analyses, and advanced imaging methods. Here, we review recent findings on FRC-immune cell interaction and the elaboration of FRC development and differentiation. We discuss how imaging approaches have not only shaped our understanding of FRC biology, but have critically advanced the niche concept of immune cell maintenance and control of immune reactivity.

Tissue niches and immunopathology through the lens of spatial tissue profiling techniques.

Spatial organization plays a fundamental role in biology, influencing the function of biological structures at various levels. The immune system, in particular, relies on the orchestrated interactions of immune cells with their microenvironment to mount protective or pathogenic immune responses. The COVID-19 pandemic has underscored the significance of studying immunity within target organs to understand disease progression and severity. To achieve this, multiplex histology and spatial transcriptomics have proven indispensable in providing a spatial context to protein and gene expression patterns. By combining these techniques, researchers gain a more comprehensive understanding of the complex interactions at the cellular and molecular level in distinct tissue niches, key functional units modulating health and disease. In this review, we discuss recent advances in spatial tissue profiling techniques, highlighting their advantages over traditional histopathology studies. The insights gained from these approaches have the potential to revolutionize the diagnosis and treatment of various diseases including cancer, autoimmune disorders, and infectious diseases. However, we also acknowledge their challenges and limitations. Despite these, spatial tissue profiling offers promising opportunities to improve our understanding of how tissue niches direct regional immunity, and their relevance in tissue immunopathology, as a basis for novel therapeutic strategies and personalized medicine.

Perivascular stromal cells: Directors of tissue immune niches.

Perivascular niches are specialized microenvironments where stromal and immune cells interact with vasculature to monitor tissue status. Adventitial perivascular niches surround larger blood vessels and other boundary sites, supporting collections of immune cells, stromal cells, lymphatics, and neurons. Adventitial fibroblasts (AFs), a subtype of mesenchymal stromal cell, are the dominant constituents in adventitial spaces, regulating vascular integrity while organizing the accumulation and activation of a variety of interacting immune cells. In contrast, pericytes are stromal mural cells that support microvascular capillaries and surround organ-specific parenchymal cells. Here, we outline the unique immune and non-immune composition of perivascular tissue immune niches, with an emphasis on the heterogeneity and immunoregulatory functions of AFs and pericytes across diverse organs. We will discuss how perivascular stromal cells contribute to the regulation of innate and adaptive immune responses and integrate immunological signals to impact tissue health and disease.

Uncovering widespread Anthropocene dietary shifts in Chinese large mammalian herbivores.

The Anthropocene's human-dominated habitat expansion endangers global biodiversity. However, large mammalian herbivores experienced few extinctions during the 20th century, hinting at potentially overlooked ecological responses of a group sensitive to global change. Using dental microwear as a proxy, we studied large herbivore dietary niches over a century across mainland China before (1880s-1910s) and after (1970s-1990s) the human population explosion. We uncovered widespread and significant shifts (interspecific microwear differences increased and intraspecific microwear dispersion expanded) within dietary niches linked to geographical areas with rapid industrialization and population growth in eastern China. By contrast, in western China, where human population growth was slower, we found no indications of shifts in herbivore dietary niches. Further regression analysis links the intensity of microwear changes to human land-use expansion. These analyses highlight dietary adjustments of large herbivores as a likely key factor in their adaptation across a century of large-scale human-driven changes.

Microevolution of Candida glabrata (Nakaseomyces glabrata) during an infection.

Candida glabrata (Nakaseomyces glabrata) is an emergent and opportunistic fungal pathogen that colonizes and persists in different niches within its human host. In this work, we studied five clinical isolates from one patient (P7), that have a clonal origin, and all of which come from blood cultures except one, P7-3, obtained from a urine culture. We found phenotypic variation such as sensitivity to high temperature, oxidative stress, susceptibility to two classes of antifungal agents, and cell wall porosity. Only isolate P7-3 is highly resistant to the echinocandin caspofungin while the other four isolates from P7 are sensitive. However, this same isolate P7-3, is the only one that displays susceptibility to fluconazole (FLC), while the rest of the isolates are resistant to this antifungal. We sequenced the PDR1 gene which encodes a transcription factor required to induce the expression of several genes involved in the resistance to FLC and found that all the isolates encode for the same Pdr1 amino acid sequence except for the last isolate P7-5, which contains a single amino acid change, G1099C in the putative Pdr1 transactivation domain. Consistent with the resistance to FLC, we found that the CDR1 gene, encoding the main drug efflux pump in C. glabrata, is highly overexpressed in the FLC-resistant isolates, but not in the FLC-sensitive P7-3. In addition, the resistance to FLC observed in these isolates is dependent on the PDR1 gene. Additionally, we found that all P7 isolates have a different proportion of cell wall carbohydrates compared to our standard strains CBS138 and BG14. In P7 isolates, mannan is the most abundant cell wall component, whereas ß-glucan is the most abundant component in our standard strains. Consistently, all P7 isolates have a relatively low cell wall porosity compared to our standard strains. These data show phenotypic and genotypic variability between clonal isolates from different niches within a single host, suggesting microevolution of C. glabrata during an infection.

Repeated migration, interbreeding and bottlenecking shaped the phylogeography of the selfing grass Brachypodium stacei.

Brachypodium stacei is the most ancestral lineage in the genus Brachypodium, a model system for grass functional genomics. B. stacei shows striking and sometimes contradictory biological and evolutionary features, including a high selfing rate yet extensive admixture, an ancient Miocene origin yet with recent evolutionary radiation, and adaptation to different dry climate conditions in its narrow distribution range. Therefore, it constitutes an ideal system to study these life history traits. We studied the phylogeography of 17 native circum-Mediterranean B. stacei populations (39 individuals) using genome-wide RADseq SNP data and complete plastome sequences. Nuclear SNP data revealed the existence of six distinct genetic clusters, low levels of intra-population genetic diversity and high selfing rates, albeit with signatures of admixture. Coalescence-based dating analysis detected a recent split between crown lineages in the Late Quaternary. Plastome sequences showed incongruent evolutionary relationships with those recovered by the nuclear data, suggesting interbreeding and chloroplast capture events between genetically distant populations. Demographic and population dispersal coalescent models identified an ancestral origin of B. stacei in the western-central Mediterranean islands, followed by an early colonization of the Canary Islands and two independent colonization events of the eastern Mediterranean region through long-distance dispersal and bottleneck events as the most likely evolutionary history. Climate niche data identified three arid niches of B. stacei in the southern Mediterranean region. Our findings indicate that the phylogeography of B. stacei populations was shaped by recent radiations, frequent extinctions, long-distance dispersal events, occasional interbreeding, and adaptation to local climates.

Frontiers of Neurodegenerative Disease Treatment: Targeting Immune Cells in Brain Border Regions.

Neurodegenerative diseases (NDs) demonstrate a complex interaction with the immune system, challenging the traditional view of the brain as an "immune-privileged" organ. Microglia were once considered the sole guardians of the brain's immune response. However, recent research has revealed the critical role of peripheral immune cells located in key brain regions like the meninges, choroid plexus, and perivascular spaces. These previously overlooked cells are now recognized as contributors to the development and progression of NDs. This newfound understanding opens doors for pioneering therapeutic strategies. By targeting these peripheral immune cells, we may be able to modulate the brain's immune environment, offering an alternative approach to treat NDs and circumvent the challenges posed by the blood-brain barrier. This comprehensive review will scrutinize the latest findings on the complex interactions between these peripheral immune cells and NDs. It will also critically assess the prospects of targeting these cells as a ground-breaking therapeutic avenue for these debilitating disorders.

Morpho-histology of co-occurrence of somatic embryos, shoots, and inflorescences within a callus of Limonium 'Misty Blue'.

This is the first attempt to report the co-occurrence of somatic embryos, shoots, and inflorescences and their sequential development from stem cell niches of an individual callus mass through morpho-histological study of any angiosperm. In the presence of a proper auxin/cytokinin combination, precambial stem cells from the middle layer of a compact callus, which was derived from the thin cell layer of the inflorescence rachis of Limonium, expressed the highest level of totipotency and pluripotency and simultaneously developed somatic embryos, shoots, and inflorescences. This study also proposed the concept of programmed cell death during bipolar somatic embryo and unipolar shoot bud pattern formation. The unique feature of this research was the stepwise histological description of in vitro racemose inflorescence development. Remarkably, during the initiation of inflorescence development, either a unipolar structure with open vascular elements or an independent bipolar structure with closed vascular elements were observed. The protocol predicted the production of 6.6 ± 0.24 and 7.4 ± 0.24 somatic embryos and shoots, respectively, from 400 mg of callus, which again multiplied, rooted, and acclimatised. The plants' ploidy level and genetic fidelity were assessed randomly before acclimatisation by flow cytometry and inter simple sequence repeats (ISSR) marker analysis. Finally, the survivability and flower quality of the regenerated plants were evaluated in the field.

Generational Specific Recruitment of Arsenic- and Antimony-Reducing Microorganisms in Plant Root-Associated Niches for Adapting to Metalloid-Metal Pollution.

The recruitment of microorganisms by plants can enhance their adaptability to environmental stressors, but how root-associated niches recruit specific microorganisms for adapting to metalloid-metal contamination is not well-understood. This study investigated the generational recruitment of microorganisms in different root niches of Vetiveria zizanioides (V. zizanioides) under arsenic (As) and antimony (Sb) stress. The V. zizanioides was cultivated in As- and Sb-cocontaminated mine soils (MS) and artificial pollution soils (PS) over two generations in controlled conditions. The root-associated microbial communities were analyzed through 16S rRNA, arsC, and aioA gene amplicon and metagenomics sequencing. V. zizanioides accumulated higher As(III) and Sb(III) in its endosphere in MS in the second generation, while its physiological indices in MS were better than those observed in PS. SourceTracker analysis revealed that V. zizanioides in MS recruited As(V)- and Sb(V)-reducing microorganisms (e.g., Sphingomonales and Rhodospirillaceae) into the rhizoplane and endosphere. Metagenomics analysis further confirmed that these recruited microorganisms carrying genes encoding arsenate reductases with diverse carbohydrate degradation abilities were enriched in the rhizoplane and endosphere, suggesting their potential to reduce As(V) and Sb(V) and to decompose root exudates (e.g., xylan and starch). These findings reveal that V. zizanioides selectively recruits As- and Sb-reducing microorganisms to mitigate As-Sb cocontamination during the generational growth, providing insights into novel strategies for enhancing phytoremediation of metalloid-metal contaminants.

Reactive oxygen species downregulate dystroglycans in the megakaryocytes of rats with arterial hypertension.

Hypertension is a multifactorial disease characterized by vascular and renal dysfunction, cardiovascular remodeling, inflammation, and fibrosis, all of which are associated with oxidative stress. We previously demonstrated cellular reactive oxygen species (ROS) imbalances may impact the structural and biochemical functions of blood cells and reported downregulation of ß-dystroglycan (ß-Dg) and overexpression of the epithelial sodium channel (ENaC) contribute to the pathophysiology of hypertension. In this study, we aimed to determine the expression of dystroglycans (Dg) and ENaC in platelet progenitors (megakaryocytes) and their surrounding niches. Thin sections of bone marrow from 5- and 28-week-old spontaneous hypertensive rats (SHR) were compared to age-matched normotensive rats (WKY). Cytometry and immunohistochemical assays demonstrated an oxidative environment in SHR bone marrow, characterized by high levels of myeloperoxidase and 3-nitrotyrosine and downregulation of peroxiredoxin II. In addition, transmission electron micrography and confocal microscopy revealed morphological changes in platelets and Mgks from SHR rats, including swollen mitochondria. Quantitative qRT-PCR assays confirmed downregulation of Dg mRNA and immunohistochemistry and western-blotting validated low expression of ß-Dg, mainly in the phosphorylated form, in Mgks from 28-week-old SHR rats. Moreover, we observed a progressive increase in ß-1 integrin expression in Mgks and extracellular matrix proteins in Mgk niches in SHR rats compared to WKY controls. These results indicate accumulation of ROS promotes oxidative stress within the bone marrow environment and detrimentally affects cellular homeostasis in hypertensive individuals.

Spatial and temporal patterns of phytoplankton community succession and characteristics of realized niches in Lake Taihu, China.

Understanding the dynamics and succession of phytoplankton in large lakes can help inform future lake management. The study analyzed phytoplankton community variations in Lake Taihu over a 21-year period, focusing on realized niches and their impact on succession. The study developed a niche periodic table with 32 niches, revealing responses to environmental factors and the optimal number of niches. Results showed that the phytoplankton in Lake Taihu showed significant spatial and temporal heterogeneity, with biomass decreasing as one moved from the northwest to the southeast and expanding towards central lake area, and towards autumn and winter. Different phytoplankton groups in Lake Taihu occupied realized niches shaped by temperature, nitrate, and phosphate. To predict the response of eutrophic freshwater lake ecosystems to human activities and climate change, it is critical to interpret the law of phytoplankton bloom and niche succession.

Impact of dual Bt-transgenic maize (2A7) on soil microbial communities and enzyme activities: A comparative study with control variety Z58.

The impacts of transgenic crops on soil microbiology and fertility are critical in determining their biosafety. While transgenic crops can alter soil microbes, their effects are often context-dependent; therefore, the ecological importance of these changes remains a topic of ongoing research. Using high-throughput sequencing, we investigated the effects of Bacillus thuringiensis (Bt) maize expressing the mcry1Ab and mcry2Ab genes (2A7) on soil nutrient dynamics, as well as the diversity and function of soil microbial communities, including bacteria and fungi, within different soil compartments. Our findings revealed a plant-shaped rhizosphere (RS) microbial community as a result of the selective recruitment of microorganisms from the surrounding environment. The transgene insertion had a significant impact on the RS niche, and several species eventually became associated with Z58 and 2A7 plants. For example, Neocosmospora rubicola fungal and Pantoea dispersa bacterial microorganisms were significantly decreased in the dual Bt-transgenic 2A7 rhizosphere but enriched in the Z58 rhizospheres. The activity of soil enzymes such as urease, invertase, and alkaline phosphatase was boosted by Bt-transgenic 2A7. LefSe analysis identified significant bacterial and fungal biomarker species that were responsible for the differential effects of Bt-transgenic 2A7 and control Z58 within rhizosphere soils. Mantel analysis further demonstrated that the root exudates of 2A7 altered nutrient-acquisition enzymes by influencing biomarker taxa. PICRUSt2 functional characterization revealed a significantly higher abundance of the phosphate-starvation-inducible protein in control Z58 than in Bt-transgenic 2A7. Furthermore, taxonomy, alpha (Shannon diversity), and beta diversity analyses all revealed niche-driven microbial profile differentiation. Niche partitioning also had a significant impact on N- and P-related COGs as well. Our findings suggests that Bt-transgenic 2A7 modulates rhizosphere microbial communities by affecting biomarker taxa and soil enzyme activity. These findings will promote sustainable agriculture practices by advancing our knowledge of the ecological effects of Bt crops on soil microbial communities.

From Local Farms to Supermarket Foods: The Story of the Homogenization of the Argentine Diet Told by the Isotope Ratios of Modern Teeth.

OBJECTIVES: Nutritional changes over the last century, driven by globalization, hypermarketization, and malnutrition, are global in scale. Large countries in the Global South might be resilient to dietary homogenization due to their natural diversity of regions and ecosystems, which might have prevented the adoption of supermarket diets. Argentina has a wide array of ecosystems and historically different subsistence diets dependent on regional characteristics. We analyzed the spatiotemporal variation of stable isotope values in Argentina using modern teeth to test for regional dietary patterns and its consistence over time. MATERIALS AND METHODS: We collected teeth from voluntary donors born between 1940 and 2010, from 72 locations across Argentina. A total of 119 teeth were analyzed for the markers δ13Cdentine, δ13Cenamel, δ15N, and δ34S. A reconstruction of isotopic niches was performed to estimate dietary patterns across different regions and time periods. RESULTS: This study is the first to analyze changes in modern dietary patterns in Argentina using isotopic data measured in contemporary teeth. We showed latitudinal, longitudinal, and temporal differences in isotopic values, reflecting the variation in available resources within the country. Changes in the diet were observed over time, including declining δ15N values, a reduction in δ34S range, and a trend toward homogenization of δ13Cenamel values. Conversely, δ13Cdentine values remained constant over time, maintaining latitudinal patterns and regional differences across regions. DISCUSSION: This study increases our understanding of modern population dietary patterns both spatially and over the last 70 years. Our findings suggest that the Argentine population has shifted toward a supermarket diet in recent years.

Effects of forest fragmentation on the dietary ecology and activity of a nocturnal lemur community in North West Madagascar.

Deforestation and habitat fragmentation is the primary threat to primate populations. The primates that live within degraded and anthropogenically disturbed habitats typical of fragmented landscapes have to cope with lower availability of resources in comparison to primates in continuous, undisturbed forests. While some species are sensitive to forest fragmentation, some evidence exists to suggest that primates can alter their behavior and adapt to such changes, which enables their survival in suboptimal habitat. In this study, we assessed how forest fragmentation and its associated edge-effects impact the feeding ecology and activity levels of a nocturnal primate community in the Sahamalaza-Iles Radama National Park, North West Madagascar. From March 06, 2019 to May 17, 2022, we collected data on tree and invertebrate phenology at our study site, and feeding ecology and activity for 159 lemur individuals from four species. Fruit and flower availability varied significantly between continuous and fragmented forest, and between forest core and edge areas, with continuous forest exhibiting higher continuous fruit and flower availability. Lemur feeding ecology varied significantly too, as the feeding niches of all four species were significantly different between continuous and fragmented forest and between core and edge areas. However, lemur activity levels were mostly consistent among all forest areas. The results of this study suggest that nocturnal lemurs are able to adapt their dietary ecology in response to the available food sources within their habitat. Due to this flexible ecology and dietary plasticity, the lemurs do not need to significantly alter their behavior in different environments to fulfill their dietary needs. While nocturnal lemurs demonstrate adaptability and flexibility to degraded habitat, it is unclear how far this plasticity will stretch considering that Madagascar's forests are still being cleared at an alarming rate. Urgent conservation action is therefore needed to ensure the future of lemur habitat.

Network ecology: Tie fitness in social context(s).

Social relations are embedded in material, cultural, and institutional settings that affect network dynamics and the resulting topologies. For example, romantic entanglements are subject to social and cultural norms, interfirm alliances are constrained by country-specific legislation, and adolescent friendships are conditioned by classroom settings and neighborhood effects. In short, social contexts shape social relations and the networks they give rise to. However, how and when they do so remain to be established. This paper presents network ecology as a general framework for identifying how the proximal environment shapes social networks by focusing interactions and social relations, and how these interactions and relations in turn shape the environment in which social networks form. Tie fitness is introduced as a metric that quantifies how well particular dyadic social relations would align with the setting. Using longitudinal networks collected on two cohorts each in 18 North American schools, i.e., 36 settings, we develop five generalizable observations about the time-varying fitness of adolescent friendship. Across all 252 analyzed networks, tie fitness predicted new tie formation, tie longevity, and tie survival. Dormant fit ties cluster in relational niches, thereby establishing a resource base for social identities competing for increased representation in the relational system.