Biology subjects

Maeda, S.

Publications and source records attributed to Maeda, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Ancient Ryukyu Jomon contributed to past and current genetic structure of Japanese populations

Characterized by the earliest use of pottery, the Jomon culture was a unique Neolithic culture that spread throughout the Japanese Archipelago. Previous archaeological evidence suggests that Jomon hunter-gatherers colonized the southernmost islands, the Ryukyu Archipelago, by approximately 7,000 years before present (YBP). However, genetic characteristics of the Ryukyu Jomon population and its contribution to the modern population have not been elucidated yet. In this study, we newly sequenced 273 modern and 25 ancient (6,700-900 YBP) whole genomes collected across the Ryukyu Archipelago. Our analysis demonstrated a genetic differentiation between the Hondo (Japanese mainland) and Ryukyu Jomon, dating back to [~]6,900 YBP. After the divergence from the Hondo Jomon, the Ryukyu Jomon experienced severe bottlenecks, with an effective population size of [~]2,000. Admixture between the Ryukyu Jomon and migrants from the historic Hondo population occurred [~]1,000 YBP, which corresponds to the widespread adoption of iron tools and agriculture in the Central Ryukyus. Different demographic histories between modern Hondo and Ryukyu populations resulted in different rates of Jomon ancestry in these populations. By providing a new perspective on the peopling of the Ryukyu Archipelago, this study significantly enhances our understanding of cultural transitions in the region.

evolutionary biology↗

bioRxiv2026

Identification of bacterial candidates that promote the growth of the seagrass Zostera marina

BackgroundGlobally, seagrass ecosystems are threatened by anthropogenic activities that are leading to increased levels of eutrophication, coastal pollution and thermal conditions. Consequently, there is a growing need to develop new approaches that work to mitigate these stressors and enhance restoration efforts in seagrass meadows. One promising strategy is to identify, isolate and characterize microbial consortia that are likely to support seagrass productivity. However, our current understanding of key microbial functions that support plant growth in marine systems is limited. Based on evidence from terrestrial plant-microbe systems, seagrass-associated bacteria are expected to provide the plant with nitrogen and phosphorus resources while detoxifying sulfur and producing phytohormones. Here, we sequenced 61 bacterial cultures isolated from the rhizosphere, rhizoplane, and endosphere of the seagrass, Zostera marina to identify a consortium of six putative plant growth promoting (PGP) candidates. ResultsOur cultivation approach using plant-based media allowed us to isolate 201 bacteria from Z. marina, which reflected 18% of the total microbial diversity of the starting inoculum. Genomic and phenotypic analyses of the 61-sequenced pure-cultures revealed that most of the sequenced taxa were able to mobilize nitrogen primarily through catabolic pathways, including denitrification (51%), dissimilatory nitrate reduction to ammonia (71%), and C-N bond cleavage (83%). Six of the isolates, which represent new lineages of Agarivorans, coded for the nitrogenase gene cassette. Additionally, 52% of the genomes had genes for sulfur and/or thiosulfate oxidation, 88.5% for phosphorus solubilization, and 60.5% for IAA production. Genomic analysis also revealed that some pathways, including denitrification and dissimilatory nitrite to ammonia DNRA, required cross-species cooperation as no one taxa contained all the genes needed to complete these metabolic pathways. Based on draft genome models and results from phenotypic assays, isolates Streptomyces sp. (Iso23 and Iso384), Mesobacillus sp (Iso127), Roseibuim sp. (Iso195), Peribacillus sp. (Iso49), and Agarivorans sp. (Iso311) represent a minimal microbial community that is likely to promote seagrass growth and enhance restoration efforts. ConclusionOur work provides a detailed genomic and phenotypic analysis of bacteria isolated from Z. marina and identifies a minimal microbial community with complementary PGP traits. Isolating, identifying and characterizing bacteria that promote seagrass growth is critical towards enhancing restoration efforts of seagrass meadows.

microbiology↗

bioRxiv2025

Structural basis of stepwise G protein activation by a viral chemokine receptor

G protein-coupled receptors (GPCRs) govern diverse cellular responses and are crucial drug targets. However, the sequence of structural events from G protein recognition to GDP release has remained elusive. Here, we leveraged the viral chemokine GPCR US28 to capture multiple activation states of the US28-Gq complex. Using cryo-electron microscopy and an engineered chemokine superagonist, we determined three distinct complex structures, capturing a GDP-bound Encounter state, the nucleotide-free Canonical state, and a putative intermediate bridging the two states, the Transition-to-Canonical state. These structures, along with simulations and functional data, provide high-resolution snapshots of a plausible G protein activation trajectory and support a stepwise conformational model for G protein activation. This activation cascade closely parallels mechanisms proposed for human GPCRs, suggesting a conserved GPCR signaling mechanism.

biophysics↗

bioRxiv2025

Epigenomic and transcriptomic germ-free ageing atlas reveals sterile inflammation as an intrinsic ageing feature

Inflammageing is a hallmark of ageing. Commensal microbiota plays crucial roles in maintaining tissue homeostasis, yet its impact on cellular ageing and inflammageing remains poorly understood. Here we present a comprehensive single-cell epigenomic and transcriptomic atlas of tissues from mice aged under specific pathogen-free (SPF) or germ-free (GF) conditions. Microbiota conferred beneficial effects in young mice but accelerated various ageing features in old, such as age-related AP-1 pathway upregulation, senescence and transcriptomic alterations, likely due to age-associated dysbiosis. Strikingly, inflammatory signatures persisted across cell types in aged GF mouse tissues, establishing sterile inflammation as an intrinsic feature of ageing. Age-associated B cells expanded equally under GF and SPF conditions, raising the possibility that they function as intrinsic, microbiota-independent drivers of inflammageing and potential therapeutic targets. The atlas provides a resource for distinguishing intrinsic ageing features from those modulated by the microbiota, illuminating mechanisms of cellular ageing and potential anti-ageing interventions. HighlightsSterile inflammation and age-associated B cell expansion are prominent intrinsic ageing features The upregulation of age-associated AP-1 pathways and senescence of alveolar macrophages are attenuated in germ-free condition Germ-free condition induces premature ageing-like features in young mouse tissues but delays ageing features in old mice across multiple cell types

genomics↗

bioRxiv2025

Noradrenergic efferent subsystems that gate traumatic social learning

Individuals experience varying magnitudes of stress in their daily lives. Although stress responses facilitate adaptive processes to cope with changing environments, severe stress can lead to traumatic learning and anxiety disorders. However, the neuronal mechanisms underlying the influence of stress severity on these processes remain unclear. Here, we show that traumatic social stress engages anatomically distinct locus coeruleus noradrenergic (LCNA) subpopulations that exhibit dynamic responses scaled to aversive salience. Using whole-brain activity and axonal projection mappings, we identified projectome subtypes of LCNA neurons, which are differentially recruited by single versus consecutive aversive social experiences. While hippocampus-projecting LCNA neurons responded to general social contacts, thalamus-projecting LCNA neurons tracked the aversive salience of social stimuli. Functional manipulations revealed a bidirectional role of thalamus-projecting LCNA neurons in social avoidance learning. These findings reveal the functional architecture of LCNA subsystems that regulate traumatic social learning via dynamic scaling to aversive salience.

neuroscience↗

bioRxiv2025

Uptake of fucosylated type I human milk oligosaccharide blocks by Bifidobacterium longum subsp. infantis

Human milk oligosaccharides (HMOs) are uniquely rich in the type 1 building block disaccharide lacto-N-biose I (LNB, Gal{beta}1,3GlcNAc), as compared to other mammals. Most HMOs are fucosylated, e.g., 1,2 and 1,4 fucosylations on LNB blocks, resulting in H type 1 (H1) and Lewis a (Lea) epitopes, respectively. The dominance of Bifidobacterium in breastfed infant guts hinges on efficient uptake of HMOs by specific ATP-binding cassette (ABC) importers. However, molecular insight into uptake of fucosylated LNB blocks is lacking. Here, we analyzed the uptake of LNB and its fucosylated H1 and Lea trisaccharides, as well as the mucin-derived disaccharide galacto-N-biose (GNB, Gal{beta}1,3GalNAc) by an ABC importer form the HMO-utilization specialist Bifidobacterium longum subsp. infantis. Structural analyses and molecular dynamics simulations explained how fucosylated and non-fucosylated LNB forms are recognized with similar affinities by the binding protein of this importer. Strikingly, we showed that two ABC importers confer to the uptake of LNB, while the Lea trisaccharide is efficiently internalized by a single importer in B. infantis. Phylogenetic and structural analyses of bifidobacterial ABC-associated binding proteins showed that the Lea clade harbors homologues possessing internal cavities, which allows for the accommodation of branched oligosaccharides. Our work provides unique insight into the evolution and molecular basis of capture and uptake of key HMO and host-derived saccharide blocks, highlighting these compounds as hitherto unexplored candidates for fortification of infant formula. ImportanceThe assembly of the gut microbiota in early life is critical to the health trajectory of human hosts. Breast feeding selects for a Bifidobacterium-rich community, adapted to efficiently utilize HMOs from mothers milk. Industrial scale production of HMOs for infant formula fortification has mainly considered fucosyllactoses, whereas fucosylated type 1 HMO blocks have hitherto not been explored. Our work sheds light on the uptake facet, central to the utilization of fucosylated HMOs with type 1 LNB building blocks. These type I blocks are efficiently internalized and assimilated by B. infantis, which has been recently shown to secrete immune-modulatory aromatic-lactate metabolites that mediate immune-priming of hosts in early life. This study contributes to our understanding of the utilization of HMOs and highlights fucosylated LNB blocks, as hitherto unexplored prebiotic candidates that support the growth of B. infantis and other beneficial bacteria in early life.

microbiology↗

bioRxiv2024

Structural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase

Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) those are the main phospholipids in eukaryotic cells. Here we present the structure of the yeast CPT1 in multiple substrate-bound states. Structural and functional analysis of these binding-sites reveal the critical residues for the DAG acyl-chain preference and the choline/ethanolamine selectivity. Additionally, we present the structure in complex with a potent inhibitor characterized in this study. The ensemble of structures allows us to propose the reaction mechanism for phospholipid biosynthesis by the family of CDP-alcohol phosphatidyltransferases (CDP-APs).

biochemistry↗

bioRxiv2023

Selective plane activation structured illumination microscopy

Resolution enhancement in structured illumination microscopy is hindered when volumetric samples are observed owing to background signals from out-of-focus planes. In this study, we utilized selective plane illumination and reversibly photoswitchable fluorescent proteins to realize structured illumination within the focal plane and eliminate the out-of-focus background. We demonstrated high-resolution fluorescence imaging of volumetric samples, including dense fluorescent objects in a cell spheroid.

biophysics↗

bioRxiv2023

Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the PKD1 gene (chrE3:g.42858112C>A, the conventional PKD1 variant). Epidemiological studies on feline ADPKD caused by the conventional PKD1 variant have been conducted in several countries, including Japan. However, they were limited to Persian cats or cats already suspected of ADPKD. There are no data on the prevalence of the conventional PKD1 variant among a wider cat population in Japan that is not limited to certain breeds or clinical backgrounds. This large-scale epidemiological study involving 1,281 cats aimed to establish a new genotyping assay to detect the conventional PKD1 variant rapidly. Among the cats examined in this study, 1.8% (23/1,281) harbored the conventional PKD1 variant. The odds of having the conventional PKD1 variant were significantly higher in Persian cats, Scottish Folds, and Exotic Shorthairs than in the other breeds. Furthermore, targeted resequencing of PKD1 was performed in cats with ADPKD and healthy cats to search for new variants that may be involved in ADPKD. We identified four variants unique to ADPKD cats that were not found in healthy cats, all of which were in exon 15. This indicates that variants in exon 15 of PKD1, in addition to the conventional variant in exon 29, are key factors in the pathogenesis of ADPKD in cats.

molecular biology↗

bioRxiv2023

Protective role of protease-activated receptor-2 in anaphylaxis model mice

Anaphylaxis is a severe life-threatening hypersensitivity reaction induced by mast cell degranulation. Among the various mediators of mast cells, little is known about the role of tryptase. Therefore, we aimed to elucidate the role of protease-activating receptor-2 (PAR-2), a receptor activated by tryptase, in murine anaphylactic models using PAR-2-deficient mice and newly generated tryptase-deficient mice. Anaphylaxis was induced by IgE-dependent and IgE-independent mast cell degranulation in mice. PAR-2 deficiency exacerbated the decrease in body temperature and hypotension during anaphylaxis; however, the number of skin mast cells, degree of mast cell degranulation, and systemic and local vascular hyperpermeability were comparable in PAR-2 knockout and wild-type mice. Nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), is an indispensable vasodilator in anaphylaxis. In the lungs of anaphylactic mice, PAR-2 deficiency promoted eNOS expression and phosphorylation, suggesting a protective effect of PAR-2 against anaphylaxis by downregulating eNOS activation and expression. Based on the hypothesis that the ligand for PAR-2 in anaphylaxis is mast cell tryptase, tryptase-deficient mice were generated using CRISPR-Cas9. In wild-type mice, the PAR-2 antagonist exacerbated the body temperature drop due to anaphylaxis; however, the effect of the PAR-2 antagonist was abolished in tryptase-deficient mice. These results suggest that tryptase is a possible ligand of PAR-2 in anaphylaxis and that the tryptase/PAR-2 pathway attenuates the anaphylactic response in mice.

molecular biology↗

bioRxiv2022

Structural basis for RNA slicing by a plant Argonaute

Argonaute (AGO) proteins use small RNAs to recognize transcripts targeted for silencing in plants and animals. Many AGOs possess an endoribonuclease activity termed RNA slicing, which catalyzes rapid turnover of target RNAs. The nuclease activity of Thermus thermophilus AGO (TtAgo)1,2 is often used as a model for RNA slicing, but how well DNA-guided slicing by this bacterial thermophile resembles RNA-guided slicing by eukaryotic AGOs is not known. We present cryo-EM structures of the Arabidopsis thaliana Argonaute10 (AtAgo10)-guide RNA complex with and without a target RNA representing a slicing substrate. Like TtAgo, AtAgo10 conformation expands in response to target binding. However, the AtAgo10-guide-target complex adopts slicing-competent and -incompetent conformations that are distinct from structures of TtAgo. AtAgo10 slicing activity is licensed by docking target (t) nucleotides t9-t13 into a surface channel containing the AGO endoribonuclease active site. A {beta}-hairpin, conserved in the L1 domain of eukaryotic AGOs, secures the t9-t13 segment and coordinates t9-t13 docking with extended guide-target pairing, preventing the complex from becoming trapped in slicing-incompetent conformations. Results show the mechanism for achieving RNA slicing in eukaryotes is distinct from that of bacteria and provide insights for controlling small interfering RNA (siRNA) potency.

molecular biology↗

bioRxiv2022

The Nse5/6-like SIMC1-SLF2 Complex Localizes SMC5/6 to Viral Replication Centers

The human SMC5/6 complex is a conserved guardian of genome stability and an emerging component of antiviral responses. These disparate functions likely require distinct mechanisms of SMC5/6 regulation. In yeast, Smc5/6 is regulated by its Nse5/6 subunits, but such regulatory subunits for human SMC5/6 are poorly defined. Here, we identify a novel SMC5/6 subunit called SIMC1 that contains SUMO interacting motifs (SIMs) and an Nse5-like domain. We isolated SIMC1 from the proteomic environment of SMC5/6 within polyomavirus large T antigen (LT)-induced subnuclear compartments. SIMC1 uses its SIMs and Nse5-like domain to localize SMC5/6 to polyomavirus replication centers (PyVRCs) at SUMO-rich PML nuclear bodies. SIMC1s Nse5-like domain binds to the putative Nse6 orthologue SLF2 to form an anti-parallel helical dimer resembling the yeast Nse5/6 structure. SIMC1-SLF2 structure-based mutagenesis defines a conserved surface region containing the N-terminus of SIMC1s helical domain that regulates SMC5/6 localization to PyVRCs. Furthermore, SLF1, which recruits SMC5/6 to DNA lesions, binds SLF2 analogously to SIMC1 and forms a distinct Nse5/6-like complex. Thus, two Nse5/6-like complexes independently regulate human SMC5/6: SIMC1-SLF2 responding to viral challenge and SLF1/2 recognizing DNA damage.

cell biology↗

bioRxiv2021

CCR4 blockade leads to clinical activity and prolongs survival in a canine model of advanced prostate cancer

Targeting regulatory T cell (Treg) infiltration is an emerging strategy for cancer immunotherapy. However, the efficacy of this strategy in advanced prostate cancer remains unclear. Here, we describe the therapeutic efficacy of this strategy in a canine model of advanced prostate cancer. We used dogs with naturally occurring prostate cancer to study the molecular mechanism underlying Treg infiltration into tumor tissues and the effect of anti-Treg treatment. We found that tumor-infiltrating Tregs were associated with poor prognosis in dogs bearing spontaneous prostate cancer. RNA sequencing and protein analyses showed that Treg infiltration was mediated by interaction between the tumor-producing chemokine, CCL17, and the receptor CCR4 expressed on Tregs. Dogs with advanced prostate cancer responded to mogamulizumab, a monoclonal antibody targeting CCR4, with improved survival and low incidence of clinically relevant adverse events. Exploratory analyses showed urinary CCL17 concentration and BRAFV595E mutation to be independently predictive of the response to mogamulizumab. Analysis of a publicly available transcriptomic dataset of human prostate cancer showed that the CCL17/CCR4 axis correlated with the Treg marker, Foxp3. In silico survival analyses showed that high expression of CCL17 was associated with poor prognosis. Immunohistochemistry confirmed that tumor-infiltrating Tregs expressed CCR4 in human patients with prostate cancer. These findings suggest that anti-Treg treatment through the blocking of CCR4 is a promising therapeutic approach for advanced prostate cancer. One Sentence SummaryTargeting regulatory T cell infiltration by CCR4 blockade induces objective responses and improves survival in a canine model of prostate cancer.

cancer biology↗

bioRxiv2021

The dynamics of cell-free DNA from urine and blood after a full marathon

PurposeCell-free DNA (cfDNA) has been investigated as a minimally invasive biomarker for many diseases, particularly cancer. An increase in cfDNA has been observed during exercise. Neutrophil extracellular traps (NETs) may be the origin of cfDNA in response to acute exercise, but the mechanisms of generation of cfDNA during exercise remain unclear. In this study we investigated the dynamics of serum and urinary cfDNA levels and determined the relevance of other biomarkers to serum and urinary cfDNA levels and fragment size after a full marathon. MethodsSamples were collected from 23 healthy male subjects. Blood and urine samples were collected before and immediately, two hours, and one day after the full marathon. The measurements included serum and urinary cfDNA, creatine kinase, myoglobin, creatinine, white blood cells, platelets, and lactoferrin from blood, and amylase, albumin, and creatinine from urine. ResultsSerum and urinary cfDNA levels increased after a full marathon. Creatine kinase, myoglobin, and creatinine in blood, and albumin and creatinine in urine also increased significantly after a full marathon. Serum cfDNA showed peak values about 180 bp after the full marathon. Values over 1000 bp were present at two hours post-marathon. Urinary cfDNA showed peak values from 35 bp to 50 bp after the full marathon. Values over 1000 bp appeared at Immediately and two hours post marathon. ConclusionThis study revealed that both serum and urinary cfDNA levels transiently increased after a full marathon. In addition, these cfDNA fragment varied in size.

physiology↗

bioRxiv2020

Master Transcription Factors Regulate the DNA Methylation Landscape During Hepatocyte Differentiation

BackgroundHepatocytes are the dominant cell type of the human liver, with functions in metabolism, detoxification, and in producing secreted proteins. During the process of hepatocyte differentiation, gene regulation and master transcription factors have been extensively investigated, whereas little is known about how the epigenome is regulated, particularly the dynamics of DNA methylation, and the upstream factors that have critical roles. ResultsBy examining changes in the transcriptome and the methylome during in vitro hepatocyte differentiation, we identified putative DNA methylation-regulating transcription factors, which are likely involved in DNA demethylation and maintenance of hypo-methylation in a differentiation stage-specific manner. Of these factors, we further reveal that GATA6 induces DNA demethylation together with chromatin activation at a binding-site-specific manner during endoderm differentiation. ConclusionsThese results provide an insight into the spatiotemporal regulatory mechanisms exerted on the DNA methylation landscape by transcription factors, and uncover a new role for transcription factors in early liver development.

genomics↗

bioRxiv2020

Integrated Collection of Stem Cell Bank data, a data portal for standardized stem cell information

The last decade has witnessed an extremely rapid increase in the number of newly established stem cell lines. However, due to the lack of a standardized format, data exchange among stem cell line resources has been challenging, and no system can search all stem cell lines across resources worldwide. To solve this problem, we have developed Integrated Collection of Stem Cell Bank data (ICSCB) (http://icscb.stemcellinformatics.org/), the largest database search portal for stem cell line information, based on the standardized data items and terms of the MIACARM framework. Currently, ICSCB can retrieve >16,000 cell lines from four major data resources in Europe, Japan, and the United States. ICSCB is automatically updated to provide the latest cell line information, and its integrative search helps users collect cell line information for over 1,000 diseases including many rare diseases worldwide, which has been a formidable task, thereby distinguishing itself from other database search portals.

bioinformatics↗

bioRxiv2020

First and broad detection of three typical carbapenemase genes on the surfaces of commercially available spices worldwide and isolation of complete NDM-1 genes from black pepper, cumin, and clove

The spread of multidrug-resistant bacteria, particularly those producing carbapenemases, has become a major public health concern. The presence of carbapenemase genes has primarily been reported in clinical samples, whereas the presence of these genes in commercially available foods has insufficiently been studied despite its growing importance. The present study aimed to detect and characterize carbapenemase genes (blaNDM, blaIMP, blaKPC, and blaOXA-48-like) on the surfaces of commercially available spices using PCR to amplify conserved regions of these genes. It was revealed that DNAs of these genes are commonly present (13 genes/29 samples) on spices derived from at least 9 different countries. This is the first detection of any carbapenemase gene on eight spices (black pepper, cumin, clove, cardamom, mustard, caraway, parsley, and rosemary) among these. This is also the first detection of the blaIMP and blaNDM as well as the broad detection of the blaOXA-48-like on spices. We also isolated complete, functional blaNDM-1 genes from three spices (black pepper, cumin, and clove) up to the present.

microbiology↗

bioRxiv2019

Circulating Th17.1 cells as candidate for prediction of therapeutic response to abatacept in patients with rheumatoid arthritis: exploratory research

T helper 17.1 cells (Th17.1) are highly pathogenic T cells in inflammatory diseases. This study aimed to identify Th cell biomarkers, including the analysis of Th17.1, that predict therapeutic response to abatacept in patients with rheumatoid arthritis. The circulating Th subsets among CD4+ T lymphocytes in 40 patients with rheumatoid arthritis before abatacept treatment were determined using multicolor flow cytometry. All patients received abatacept treatment for 24 weeks, and the change in disease activity score, including 28-joint count C-reactive protein, and the responsiveness of other indices to abatacept treatment were evaluated according the European League Against Rheumatism criteria [good responders, moderate responders, and non-responders]. The correlation between the abatacept responses and the Th subsets (baseline) was analyzed. Logistic regression analysis with inverse probability weighting method was conducted to calculate odds ratio adjusted for patient characteristics. The proportion of baseline Th17.1 cells was significantly lower in patients categorized as good responders than in those categorized as non-good responders (moderate responders and non-responders; p = 0.0064). The decrease in 28-joint count C-reactive protein after 24 weeks of abatacept therapy also showed a significant negative correlation with the proportion of Th17.1 cells. The adjusted odds ratio for achieving good response in patients with baseline Th17.1 level below the median value was 14.6 (95% confidence interval, 2.9-72.3; p = 0.0021) relative to that in the remaining patients. The proportion of Th17.1 cells at baseline is a good candidate for the prediction of response to abatacept treatment. These novel findings may represent an important step in the pursuit of precision medicine.

immunology↗