Biology subjects

Atsumi, T.

Publications and source records attributed to Atsumi, T..

5 recordsLinked to original sources

bioRxiv2026

FGFR1-phosphate sensing and crystal-induced gasdermin D signaling in neutrophils drive vascular calcification in CKD

Chronic kidney disease (CKD) confers disproportionate cardiovascular risk. In non-dialysis CKD, calcification accumulates primarily within the intimal layer. Clinical studies indicate that intimal calcification correlates with hyperphosphatemia, yet the cellular and molecular pathways remain unclear. Given evidence that osteocytes sense phosphate via fibroblast growth factor receptor 1 (FGFR1), we hypothesized that FGFR1-expressing vascular immune cells, especially neutrophils, act as mediators linking high phosphate to plaque mineralization. In vitro, phosphate triggered FGFR1-dependent signaling in human and murine neutrophils, inducing neutrophil extracellular traps (NETs). Activated neutrophils promoted the depletion of Fetuin-A, a major inhibitor of calcium-phosphate complexation, creating a milieu permissive to mineral nucleation. Newly formed calcium-phosphate particles amplified NETs through gasdermin D (GSDMD), establishing a feed-forward loop that enhanced mineralization and endothelial injury in co-culture assays. Human arteriosclerotic plaques from CKD patients showed NETs markers co-localizing with calcified deposits. In vivo, pharmacological FGFR inhibition attenuated arterial intimal calcification and suppressed NET formation in CKD mice. These findings identify phosphate sensing via neutrophil FGFR1 and subsequent crystal-induced GSDMD signaling as drivers of intimal vascular calcification in CKD. Targeting phosphate-sensing pathways, NET formation, and neutrophil-driven mineralization may mitigate vascular calcification and reduce cardiovascular risk in CKD.

immunology↗

bioRxiv2026

A senescent iCAF-like fibroblast state governs therapy resistance in rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) synovitis frequently persists despite cytokine-targeted therapies, suggesting the existence of pathogenic stromal programs that sustain chronic inflammation independently of canonical immune pathways. Although synovial fibroblasts (SF) are increasingly implicated in treatment resistance, the pathogenic fibroblast states driving refractory disease and their therapeutic vulnerabilities remain poorly defined. MethodsWe integrated multimodal single-cell and spatial profiling of synovial tissue from 54 patients with RA with prospective treatment-response data and functional studies in human fibroblasts and experimental arthritis models. ResultsWe identified a C-X-C motif chemokine 12 (CXCL12)hi Apolipoprotein C1 (APOC1)+ fibroblast population selectively enriched in treatment-refractory synovitis. Spatial analyses demonstrated that these fibroblasts establish CXCL12-dependent plasmablast niches within inflamed synovium, resembling inflammatory cancer-associated fibroblasts (iCAF) that orchestrate immune cell recruitment in the tumor microenvironment. CXCL12hi APOC1+ fibroblasts exhibited a senescence-associated iCAF-like transcriptional program characterized by STAT3-C/EBP activation and APOC1 expression and were associated with poor response to TNF and IL-6 pathway inhibition. Mechanistically, APOC1 knockdown in RA-SF attenuated invasive mesenchymal behavior and disrupted senescence-associated inflammatory programs, identifying APOC1 as a central regulator of pathogenic fibroblast reprogramming. Importantly, genetic or pharmacological elimination of senescent cells ameliorated experimental arthritis and enhanced the efficacy of TNF blockade. ConclusionsThese findings implicate iCAF-like fibroblasts with senescent properties as a mechanistic driver of refractory RA synovitis and highlight stromal senescence programs as preclinically actionable therapeutic targets beyond cytokine inhibition.

immunology↗

bioRxiv2021

State-Anxiety Modulates the Effect of Emotion Cues on Visual Temporal Sensitivity in Autism Spectrum Disorder

Atypical processing of stimulus inputs across a range of sensory modalities in autism spectrum disorders (ASD) are widely reported. Sensory processing is known to be influenced by bodily internal states such as physiological arousal and anxiety. Since a sizeable proportion of ASD individuals reportedly have co-morbid anxiety disorders that are linked with dysregulated arousal, we investigated if face-emotion arousal cues, influenced visual sensory sensitivity (indexed by temporal resolution) in an ASD group (n=20) compared to a matched group of typically-developed individuals (TD, n=21). We asked further if emotion-cued changes in visual sensitivity associated with individual differences in state- and trait-anxiety. Participants reported the laterality of the second of two consecutive Gaussian-blob flashes in a visual temporal order judgment task (v-TOJ), demanding higher-level visual processing. The key manipulation was presenting a task-irrelevant face emotion cue briefly at unexpected time points preceding the task-relevant flashes. Disgust vs Neutral emotion signals enhanced the visual temporal resolution in ASD individuals. Furthermore, individual state-anxiety scores correlated with the emotion-cued change of temporal resolution (Disgust vs Neutral) in the ASD group. Both these effects were absent in the TD group. The results show that individual state-anxiety levels significantly modulate the effect of emotions on visual temporal sensitivity in ASD individuals, which was absent in our TD sample. The findings support a nuanced approach to understand the disparate sensory features in ASD individuals, by factoring in the interplay of the individual reactivity to environmental affective information and the severity of anxiety.

neuroscience↗

bioRxiv2020

Temporal resolution relates to sensory hyperreactivity independently of stimulus detection sensitivity in individuals with autism spectrum disorder

BackgroundResearchers have been focused on perceptual characteristics of autism spectrum disorder (ASD) in terms of sensory hyperreactivity. Previously, we demonstrated that temporal resolution, which is the accuracy in differentiating the order of two successive vibrotactile stimuli, is associated with the severity of sensory hyperreactivity (Ide et al. 2019). Herein, we examined whether an increase in the perceptual intensity of a tactile stimulus, despite its short duration, is derived from high temporal resolution and a high frequency of sensory temporal summation. MethodSixteen participants with ASD and fifteen typically developing (TD) participants performed two psychophysical experimental tasks, and we evaluated the detectable duration of vibrotactile stimuli with the same amplitude and temporal resolution. Sensory hyperreactivity was estimated using a self-reported questionnaire. ResultsThere was no relationship between temporal resolution and the duration of detectable stimuli in either group. However, the ASD group showed more severe sensory hyperreactivity in daily life than the TD group did, and ASD participants with severe sensory hyperreactivity tended to have high temporal resolution but not high sensitivity for detectable duration. ConclusionContrary to our hypothesis, there might be different processing between temporal resolution and sensitivity for stimulus detection. Sensory reactivity in daily life would not be based on sensitivity for stimulus detection measured in an experimental task, and we suggest that atypical temporal processing would affect sensory reactivity in ASD. Keywords (within 6 keywords): Temporal resolution, Temporal summation, Autism spectrum disorder, Hyperreactivity, Gap detection

neuroscience↗

bioRxiv2020

Decreased utilization of allocentric coordinates during reaching movement in individuals with autism spectrum disorder

Despite numerous reports of abnormalities in limb motor controls in spatial orientation in individuals with autism spectrum disorder (ASD), the underlying mechanisms have not been elucidated. We studied the influence of allocentric coordinates on ongoing reaching movements, which has been reported to strongly affect the reaching movements of typically developing (TD) individuals. ASD and TD participants observed a target presented randomly on one of the four corners of a frame on a screen. After it disappeared, another frame was presented slightly shifted leftward/rightward. The participants touched the memorized position of the target relatively congruent with a reference frame (allocentric condition) or ignoring it (egocentric condition). Results suggested that touch positions were less affected by shift directions of reference frame in the allocentric condition in ASD participants, so that they tended to reach in egocentric manner. Our findings demonstrate that decreased utilization of visual landmarks in ongoing movement may underlie motor disabilities in autism.

neuroscience↗