Biology subjects

Lira, S.

Publications and source records attributed to Lira, S..

7 recordsLinked to original sources

bioRxiv2026

Immune cells adapt to distinct stem cell niches to govern tissue homeostasis

Summary ParagraphIn adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness under homeostasis and stress. Key components of these niches are immune cells, which classically protect the host against external and internal threats. Whether and how stem cell:immune cell crosstalk contributes to normal tissue biology remains less clear. Here, we discover functional adaptation of resident lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-{beta} and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche that controls microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain continuous stem cell reconstitution of the skins barrier. Concomitantly, they express the immune checkpoint protein LAG-3, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, dermal lymphocytes restore the imbalance by colonizing and adapting to their new niche. Our findings unveil functional specialization and homeostatic resilience of immune-stem cell niches, each tailored to suit the demands of distinct tissue microenvironments.

immunology↗

bioRxiv2025

Trends in stomatal density and size in maize hybrids representing 100 years of long-term breeding for yield

Maize hybrid breeding started over 100 years ago, has increased yield and vigor through improved genetics in conjunction with increased fertilizer and pesticide use, planting density, and agricultural mechanization. Stomata are expected to change in response to rising atmospheric CO2 concentration and average temperature anomalies ({degrees}C). Yet, the impact of long-term maize breeding over the past century on stomatal traits and their responses to climate factors remains poorly understood. We evaluated stomatal traits at the seedling stage in 27 maize hybrids released from 1920 to 2022, grown under controlled conditions. Modern hybrids (2013 - 2022) had a smaller total stomatal pore area (9.17 x 108 m2) than (1920 - 2012) historical ERA hybrids (9.94 x 108 m2; p[≤] 0.001), a higher stomatal density (47.2 per mm-2) vs. historical ERA hybrids (44.5), and a smaller leaf area (17.9 cm2 vs. 20.5 cm2). No significant differences were found in the size (m2), length (m), or width (m) of stomata between the two groups. Stomatal density increased, while all other traits decreased in modern hybrids. Stomatal density was negatively correlated with stomatal size (r = -0.62), length (r = -0.57), width (r = - 0.54), and leaf area (r = -0.54). Stomatal size had a negative correlation with atmospheric CO2 concentration (r = -0.22) and average temperature anomalies ({degrees}C) (r = -0.35) in the hybrids year of release and climate proxies. In contrast, stomatal density had a positive correlation with both atmospheric CO2 concentration and average temperature anomalies ({degrees}C) (r = 0.44) in year of release. Total stomatal pore area negatively correlated with atmospheric CO2 concentration (r = -0.45) and average temperature anomalies ({degrees}C) (r = -0.36). Our study indicates that maize stomatal traits suggest inadvertent selection for key stomatal traits (density and size), total stomatal pore area (per year decline of about 0.02%) associated with yield stability and environmental adaptation. HighlightsMaize stomatal traits changed through environmental (CO2 and {degrees}C) adaptation but total stomatal pore area, effects indirectly by decreased leaf area in maize hybrids representing 100 years of long-term breeding for yield. A negative correlation was observed across 27 ERA hybrids between stomatal density and stomatal size, length, width and leaf area. Stomatal density increases while stomata size, length width and leaf area decrease per se. Over the past 100 years, the total stomatal pore area on leaves decreased, while stomatal density increased as leaf area declined, revealing a connection between these two patterns. A negative correlation was found between total stomatal pore area and atmospheric CO2 concentrations, and temperature over the past century.

genetics↗

bioRxiv2022

The novel compensatory reciprocal interplay between neutrophils and monocytes drives cancer progression

Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based genomic editing, we generated a mouse model that is deficient of all monocyte chemoattractant proteins (MCP). Using this strain, we effectively abolished monocyte infiltration in glioblastoma (GBM) and hepatocellular carcinoma (HCC) murine models, which were enriched for monocytes or neutrophils, respectively. Remarkably, eliminating monocyte chemoattraction invokes a significant compensatory neutrophil influx in GBM, but not in HCC. Single-cell RNA sequencing revealed that intratumoral neutrophils promoted proneural-to-mesenchymal transition in GBM, and supported tumor aggression by facilitating hypoxia response via TNF production. Importantly, genetic or pharmacological inhibiting neutrophil in HCC or qMCP-KO GBM extended the survival of tumor-bearing mice. Our findings emphasize the importance of targeting both monocytes and neutrophils simultaneously for cancer immunotherapy. In BriefEliminating monocyte chemoattraction invokes compensatory neutrophil influx in tumor, and vice versa, rendering current myeloid-targeted therapies ineffective. Using genetic and pharmacological approaches combined with novel mouse models of GBM and HCC, we provide credence advocating for combinational therapies aiming at inhibiting both monocytes and neutrophils simultaneously. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/500690v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@bbbae5org.highwire.dtl.DTLVardef@eb3eecorg.highwire.dtl.DTLVardef@702696org.highwire.dtl.DTLVardef@f54734_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights* Blocking monocyte chemoattraction results in increased neutrophil infiltration. * Increased neutrophil recruitment induces GBM PN to MES transition. * Inhibiting neutrophil infiltration in monocyte-deficient tumors improves mouse GBM survival. * Blocking neutrophil, but not monocyte, infiltration in HCC prolongs mouse survival.

immunology↗

bioRxiv2021

Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections

The enteric nervous system (ENS) controls several intestinal functions including motility and nutrient handling, which can be disrupted by infection-induced neuropathies or neuronal cell death. We investigated possible tolerance mechanisms preventing neuronal loss and disruption in gut motility after pathogen exposure. We found that following enteric infections, muscularis macrophages (MMs) acquire a tissue-protective phenotype that prevents neuronal loss and dysmotility during subsequent challenge with unrelated pathogens. Bacteria-induced neuroprotection relied on activation of gut-projecting sympathetic neurons and signaling via {beta}2-adrenergic receptors ({beta}2AR) on MMs. In contrast, helminth-mediated neuroprotection was dependent on T cells and systemic production of interleukin (IL)-4 and -13 by eosinophils, which induced arginase-expressing MMs that prevented neuronal loss from an unrelated infection located in a different intestinal region. Collectively, these data suggest that distinct enteric pathogens trigger a state of disease- or tissue tolerance that preserves ENS number and functionality.

immunology↗

bioRxiv2021

Can we harness digital technologies and physiology to hasten genetic gain in U.S. maize breeding?

Genetic gain in breeding programs depends on the predictive skill of genotype-to-phenotype algorithms and precision of phenotyping, both integrated with well-defined breeding objectives for a target population of environments (TPE). The integration of physiology and genomics could improve predictive skill by capturing additive and non-additive interaction effects of genotype (G), environment (E), and management (M). Precision phenotyping at managed stress environments (MSEs) can elicit physiological expression of processes that differentiate germplasm for performance in target environments, thus enabling algorithm training. Gap analysis methodology enables design of GxM technologies for target environments by assessing the difference between current and attainable yields within physiological limits. Harnessing digital technologies such as crop growth model-whole genome prediction (CGM-WGP) and gap analysis, and MSEs, can hasten genetic gain by improving predictive skill and definition of breeding goals in the U.S. maize production TPE. A half-diallel maize experiment resulting from crossing 9 elite maize inbreds was conducted at 17 locations in the TPE and 6 locations at MSEs between 2017 and 2019. Analyses over 35 families represented by 2367 hybrids demonstrated that CGM-WGP offered a predictive advantage (y) compared to WGP that increased with occurrence of drought as measured by decreasing whole-season evapotranspiration (ET; log(y) = 0.80({+/-}0.6) - 0.006({+/-}0.001) x ET; r2 = 0.59; df = 21). Predictions of unobserved physiological traits using the CGM, akin to digital phenotyping, were stable. This understanding of germplasm response to ET enables predictive design of opportunities to close productivity gaps. We conclude that enabling physiology through digital methods can hasten genetic gain by improving predictive skill and defining breeding objectives bounded by physiological realities.

plant biology↗

bioRxiv2018

IL-33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization

IL-33 is a cytokine found in the extracellular space (mature IL-33) or in the cell nucleus (full-length IL-33). Nuclear accumulation of IL-33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL-33 in IEC, we generated transgenic mice expressing full-length IL-33 in the intestinal epithelium (Vfl33 mice). Expression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33. Over-expression of full-length IL-33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL-33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL-33, we intercrossed the Vfl33 mice with ST2-deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL-33 expression, suggesting that the transcriptional effects of IL-33 on IEC are mediated by its mature, not its nuclear form.\n\nHighlightsO_LIExpression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33.\nC_LIO_LIFull-length IL-33 induced differential gene expression in IEC and LPL that was negatively associated with intestinal inflammatory diseases\nC_LIO_LIIL-33 regulated gene expression in IEC via its extracellular (mature) form not via its nuclearform.\nC_LI

immunology↗

bioRxiv2018

Gut microbiota density influences host physiology and is shaped by host and microbial factors

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohns disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.

microbiology↗