Biology subjects

Ji, C.

Publications and source records attributed to Ji, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Pathological tau leads to network hyperexcitability through neuronal-subtype-specific functional impairment

Pathological tau disrupts neuronal activity and brain function in Alzheimer s disease and other tauopathies. However, the underlying mechanisms for neuronal network dysfunction remain largely unknown. Using human inducible pluripotent stem cell (iPSC) - derived neurons, we show that the familial MAPT P301L mutation leads to neuronal network hyperexcitability. Imbalanced excitation and inhibition were attributable to neuronal subtype-specific tau pathology that was associated with different alterations of tau interactomes in excitatory versus inhibitory neurons. Suppressing enhanced excitatory synaptic transmission or blocking Ca2+ influx resulting from enhanced P301L tau/AHNAK interaction in inhibitory neurons rescued the neuronal network hyperexcitability. This study expands our understanding on how disease-causing tau mutations alter the excitatory/inhibitory balance, leading to network dysfunction in human neurons.

neuroscience↗

bioRxiv2026

CryoMV: Structure-Prior-Guided Modeling and Real-Particle Validation of Continuous Conformational Transitions in Cryo-EM

Continuous protein conformations are essential for understanding fundamental biological processes and supporting drug discovery. Although cryo-EM can resolve individual states at high resolution, recovering continuous heterogeneity from 2D particle images remains challenging. High noise, motion blur, and limited structural priors make it difficult to accurately generate and validate high-resolution continuous conformations using raw particle data. Here, we introduce cryoMV, a framework that integrates structure-prior-guided modeling with real-particle validation for continuous conformational transitions. CryoMV uses reference density maps to establish structural anchors and motion priors, models candidate transition paths between selected conformations, and transfers the learned representation to raw 2D cryo-EM particle images. Each candidate conformation is subsequently evaluated using the estimated particle poses and contrast transfer functions. Supported conformations are reconstructed through raw particle back-projection and assessed using canonical half-maps and Fourier shell correlation. On EMPIAR-10516 and EMPIAR-10345, cryoMV achieves excellent performance in terms of robustness, verifiability, and reconstruction resolution. By incorporating structure-prior modeling and evidence from the raw particles, cryoMV offers an explicit mechanism for assessing whether generated conformations are supported by experimental data and provides a practical approach to reducing model-induced artifacts in continuous cryo-EM heterogeneity analysis.

bioinformatics↗

bioRxiv2026

CryoFlex characterizes structural motion between conformations directly from cryo-EM density maps

Heterogeneous cryo-EM reconstruction methods can resolve multiple conformational states, but understanding their functional implications often requires determining which regions move between states and quantifying their displacement magnitudes. Comparing atomic models can quantify motion, but flexible regions are often incompletely modeled. Direct map comparison is limited by variable map quality and ambiguous correspondence between displaced density features. Here, we present CryoFlex, a method that estimates the direction and magnitude of structural motion directly from reconstructed density maps of selected states. The resulting motion analysis supports functional interpretation and guides downstream structure processing. CryoFlex localized and quantified structural motion across diverse map pairs, including those with incomplete atomic-model coverage or weak local density. Against C; displacements, CryoFlex achieved an endpoint error of about 1 angstrom. In separate benchmarks, it outperformed registration baselines on clean and noisy inputs. Thus, CryoFlex complements heterogeneous reconstruction workflows with direct quantification of structural motion between reconstructed states.

bioinformatics↗

bioRxiv2026

Orthoflaviviruses use diverse binding modes to engage LDLR family receptors

Orthoflaviviruses are major human pathogens that cause substantial morbidity and mortality worldwide. The viral envelope (E) mediates entry of orthoflaviviruses into host cells by interacting with cellular receptors, including members of the low-density lipoprotein receptor (LDLR) family. Here, we determined cryo-electron microscopy (cryo-EM) structures of yellow fever virus (YFV) E bound to low-density lipoprotein receptor-related protein 4 (LRP4) and LRP8, and of tick-borne encephalitis virus (TBEV) E bound to LRP8. Structural and functional studies reveal that YFV engages two low-density lipoprotein receptor class A (LA) repeats of LRP4 and LRP8 primarily through domain III (DIII) and the DI-DIII linker of its E protein, with each LA repeat making distinct contacts. In contrast, TBEV relies on a distinct surface on domain II (DII) of its E protein to interact with LRP8. Despite these differences, both viruses require engagement of two sequential receptor LA repeats for binding. Our findings identify key determinants of receptor specificity for these two orthoflaviviruses, with implications for vaccine development and therapeutic antibody targeting.

microbiology↗

bioRxiv2026

Molecular basis for chikungunya virus recognition of a mosquito-specific receptor

Alphaviruses are arthropod-borne viruses that recognize cellular receptors in both vertebrate hosts and mosquito vectors to complete their transmission cycle, yet how they maintain recognition of receptors across evolutionarily divergent host species remains unresolved. Among alphaviruses, chikungunya virus (CHIKV), which is primarily vectored in urban settings by Aedes species mosquitoes, is the most widespread, and causes explosive outbreaks that can involve hundreds of thousands to millions of cases annually. The cell adhesion protein Lachesin is a mosquito-specific cellular receptor for CHIKV and multiple other arthritogenic alphaviruses. The envelope E2-E1 glycoproteins of these alphaviruses broadly recognize Lachesin orthologs from diverse mosquito species, but not other insects or arachnids. Lachesin genetic manipulation to prevent mosquito virus infection without interfering with endogenous receptor function could have a major impact for CHIKV control. Here, we determined high-resolution cryo-electron microscopy (cryo-EM) structures of alphaviruses bound to Aedes albopictus Lachesin. Comparative analysis of Lachesin-bound CHIKV, Semliki Forest virus (SFV), and Middelburg virus (MIDV) revealed that these three genetically divergent viruses use a similar surface to recognize Lachesin domain 1, but with reorganized E2-E1 glycoprotein contact residues. We show that a soluble Ae. albopictus Lachesin receptor decoy protein blocks the E2-E1-mediated entry of CHIKV and other arthritogenic alphaviruses into mammalian cells with greater breadth than a vertebrate receptor MXRA8 decoy and protects against lethal SFV challenge and CHIKV pathogenesis in murine models. Additionally, we identified a naturally occurring single residue Lachesin polymorphism that is found in some Anopheles (malaria vector) mosquitoes, and fully ablates CHIKV E2-E1 recognition, informing strategies for mosquito-targeted genetic interventions that could prevent mosquito vector infection and virus transmission. These findings define distinct determinants of receptor binding in mosquitoes and humans for arthritogenic alphaviruses, with implications for countermeasure development and outbreak preparedness.

microbiology↗

bioRxiv2026

Cell-Type-Selective Cortical Pathology and Functional Deficits in Synucleinopathy

Aggregates of -synuclein (-syn), a hallmark of synucleinopathies, accumulate in the cerebral cortex accompanied by the emergence of motor symptoms, which are associated with altered cortical neuronal activity. However, the mechanism by which -syn pathology drives cortical network dysfunction, and how these alterations contribute to impaired motor execution and learning, remain unknown. Here, we adopted a multi-disciplinary approach to elucidate the pathophysiological characteristics in transgenic mice that express mutant human -syn, with minimal nigrostriatal degeneration. In vivo two-photon imaging revealed distinct alteration patterns in excitatory and parvalbumin (PV)-expressing inhibitory cortical neurons accompanying fine motor deficits during learning. Cell type specific ex vivo whole-cell recording further revealed selectively altered intrinsic properties in excitatory but not PV neurons, consistent with the preferential accumulation of -syn inclusions in excitatory rather than PV neurons within the same cortical region. These results indicate cell-type selective vulnerability in motor cortex of early stage synucleinopathy, leading to disrupted excitatory/inhibitory balance and dysregulated cortical plasticity, driving early-stage motor symptoms. This study provides evidence for selective vulnerability of excitatory neurons in cortical synucleinopathy.

neuroscience↗

bioRxiv2025

CryoDDM: CryoEM denoising diffusion model for heterogeneous conformational reconstruction

Heterogeneous protein reconstruction can reveal the relationship between protein dynamics and function, which represents one of the foremost challenges in cryogenic electron microscopy (cryo-EM) single-particle analysis (SPA). However, high-intensity noise results in inaccurate parameter estimation during classification and reconstruction, making it difficult to capture the subtle motions of proteins. Here, we present the Cryo-EM denoising diffusion model (CryoDDM), which denoises images while preserving high-frequency structural information, benefiting conformational heterogeneity classification and reconstruction. The image denoised by CryoDDM can be used to improve downstream analysis, enhance reconstruction resolution, discover new protein conformations, and map out conformational variations. Validated against tree diverse experimental datasets, spanning a proteasome, a membrane protein and a spike protein, our results consistently demonstrate the accuracy and superiority of CryoDDM. By guiding reconstruction with denoised images, CryoDDM enables high-resolution reconstruction of heterogeneous conformations, paving the way to illuminate fundamental questions in structural biology. The CryoDDM project are published at https://github.com/BIT-FuweiLi/CryoDDM.

bioinformatics↗

bioRxiv2025

YibaoGaussian: Generate dynamic 3D models from text using Gaussian splatting as the explicit representation

In recent years, the latest advances in the field of 3D content creation have been primarily based on neural radiation fields (NeRF). Despite significant research achievements, these methods often suffer from slow optimization speeds and high memory consumption. More importantly, these studies still mainly focus on static modeling, with very limited research on dynamic models, which restricts their practical applications. This paper proposes a method Yibaogaussian for generating dynamic 3D models from text descriptions, which can generate dynamic 3D models while ensuring efficiency and quality. Our key insight is on constructing canonical space and temporal deformation field . We build static 3D Gaussian fields in canonical space to capture the overall geometry and appearance features of a scene. By dynamically mapping the parameters of the Gaussian field to the temporal deformation field, we achieve continuous changes and natural motion of the static 3D model over time. Extensive experiments demonstrate that our proposed method offers higher efficiency and highly competitive generated quality. Notably, YibaoGaussian can generate high-quality dynamic 3D models from text descriptions in just 3 minutes, approximately 3 times faster than existing methods. This study verifies the feasibility of combining Gaussian representation and temporal deformation field in regular space, providing a new solution for text-driven dynamic 3D model generation and laying the technical foundation for multimodal applications such as digital humans, virtual reality (VR/AR), and film and television special effects.

bioengineering↗

bioRxiv2025

GSDME unlocks astrocyte-driven neurotoxicity in Alzheimer's Disease

Astrocytic calcium dysregulation and reactivity precede A{beta} deposition in amyloid-{beta} deposition in Alzheimers disease (AD) but the neurotoxic mechanisms remain unclear. We show that GSDME acts as a switch, linking MAM-mediated calcium release to astrocyte-driven neurotoxicity. Specifically, A{beta}-activated microglial signals activate astrocytic GSDME, releasing its N-terminal fragment, which targets MAMs and triggers ER calcium efflux. This induces biphasic CaMKII phosphorylation, initially boosting NRF2 defenses, then activating NF-{kappa}B-driven inflammation, shifting astrocytes from protective to toxic states. GSDME activation also drives astrocyte-derived exosomes (ADEs) to carry neurotoxic tau, proinflammatory miRNAs, and toxic lipids, propagating toxicity. GSDME deletion in AD mice reduces A{beta} burden, restores NF-{kappa}B/NRF2 balance, reprograms astrocytes and ADEs to protective states, and rescues cognition. Multi-omics profiling of serum ADEs from AD patients reveals a disease-specific signature with central neurotoxicity and peripheral immune regulation. These findings position GSDME as a promising dual diagnostic and therapeutic target for early AD invention.

neuroscience↗

bioRxiv2025

Cis-delivering releasable IL-15 superagonist enhances antitumor immunity in cold tumors by invigorating preexisting CD25+CD8+ T cells

Antibody-mediated cis-delivery and trans-delivery both direct cytokines to tumors and have been extensively investigated in clinical trials. However, a comparative analysis of their differential effects on cytokine activity is still lacking. In this study, we initially verify that cis-delivery of cytokine demonstrates a markedly stronger antitumor effect than trans-delivery, but it also exhibits certain drawbacks, including severe toxicity, insufficient activation of CD25+CD8+ T cells, and enhanced stimulation of intratumoral regulatory T cells (Tregs). To further address these issues, we developed a conditionally releasable and cis-delivering IL-15 immunocytokine (termed PMIS), which can selectively release a free IL-15 superagonist within tumors rather than immobilizing IL-15 to PD-1+ Tregs, thereby potently stimulating CD25+CD8+ T cells. Mice treated with PMIS showed significantly reduced systemic toxicities while achieving notably stronger antitumor effects. Administered either alone or in combination with other therapies, PMIS exhibits great potential for inhibiting orthotopic cold tumor and its metastases. Mechanistically, the significant activation of the pre-existing intratumoral CD25+CD8+ T cells and the improved CD25+CD8/Treg ratio contribute to the enhanced antitumor response of PMIS. These findings underscore the indispensable role of CD25+CD8+ T cells in cis-delivering IL-15 and provide a promising strategy for overcoming resistance to therapies and effectively controlling advanced cold tumors.

immunology↗

bioRxiv2025

Xenopus IgX informs engineering strategies of IgM and IgG hexamers

Polymeric immunoglobulins are essential components of the immune system in jawed vertebrates. While mammalian immunoglobulin M (IgM) typically forms a pentamer linked by the joining chain (J-chain), Xenopus laevis IgX assembles into a J-chain-independent polymer. Here, we present the cryo-electron microscopy (cryo-EM) structure of IgX, revealing its hexameric configuration. By incorporating the IgX tailpiece into human IgM, we achieved efficient IgM hexamer formation. Truncating IgMs natural tailpiece to a range of 11-16 residues also substantially enhanced hexamerization efficiency. Furthermore, introducing a shortened IgM tailpiece to IgG resulted in effective IgG hexamer formation. We further show that the engineered IgM and IgG hexamers targeting CD20 demonstrated robust complement-dependent cytotoxicity (CDC) against several B lymphoma cells. Additionally, the IgG-Fc hexamer functioned as a decoy, attenuating CDC in cell cultures. These findings deepen our understanding of polymeric immunoglobulin evolution and introduce innovative strategies for the development of IgM- and IgG-based biologics. One Sentence SummaryThe cryo-EM structure of the African clawed frog immunoglobulin IgX reveals a uniform hexameric assembly, inspiring innovative strategies for the development of therapeutic human IgM and IgG hexamers.

immunology↗

bioRxiv2025

Single-Domain Antibody-Based Autophagosome-Targeting Chimera for Tau Clearance and Motor Function Restoration in Tauopathies

Tauopathies are neurodegenerative diseases characterized by pathological tau accumulation, leading to motor and neuropsychiatric symptoms. Effective tau-targeting therapies remain a major challenge. Here, we present 1D9-LIR{Delta}TP53INP2, a single-domain antibody (sdAb)-based protein degrader that facilitates tau clearance via the autophagy-lysosomal pathway. This engineered molecule combines the anti-tau sdAb 1D9 with an LC3-interacting region (LIR{Delta}TP53INP2) to promote autophagosomal recruitment, mimicking autophagy receptors by simultaneously binding tau and LC3. In frontotemporal dementia (FTD) patient-derived neurons and JNPL3 tauopathy mice, both harboring the P301L tau mutation, 1D9-LIR{Delta}TP53INP2 significantly reduced tau levels and improved motor function in mice. These findings underscore the therapeutic potential of sdAb-based protein degraders for tauopathies. Given the challenges of brain delivery for conventional antibodies, sdAbs with enhanced brain penetration and efficacy offer a promising strategy for treatment of neurodegenerative diseases.

neuroscience↗

bioRxiv2025

Single-Cell eQTL Mapping Reveals Cell Type-Specific Genetic Regulation in Lung Cancer

Genome-wide association studies (GWAS) have identified over 50 lung cancer risk loci; however, the precise cellular context of these genetic mechanisms remains unclear due to limitations in bulk tissue eQTL analyses. Here, we present the largest single-cell eQTL atlas of human lung tissue to date, profiling 222 donors using multiplexed scRNA-seq. We identified 16,785 eQTLs across 17 cell types, with over 90% of sc-eQTLs and 59% eGene being cell-type-specific, and fewer than 23% were detectable in paired bulk datasets. Integration with GWAS for non-small cell lung cancer highlighted epithelial and immune cells as key contributors to genetic susceptibility, identifying 28 candidate genes within known risk loci and 24 in novel regions. Notably, 47% of established NSCLC susceptibility loci exhibited cell-type-specific pleiotropic genetic regulation. This study provides a valuable resource of lung sc-eQTLs and illuminates how genetic variation modulates gene expression in a cell-type-specific fashion, contributing to lung cancer susceptibility.

genetics↗

bioRxiv2024

Neuronal hypofunction and network dysfunction in a mouse model at an early stage of tauopathy

We previously reported altered neuronal Ca2+ dynamics in the motor cortex of 12-month-old JNPL3 tauopathy mice during quiet wakefulness or forced running, with a tau antibody treatment significantly restoring the neuronal Ca2+ activity profile and decreasing pathological tau in these mice 1. Whether neuronal functional deficits occur at an early stage of tauopathy and if tau antibody treatment is effective in younger tauopathy mice needed further investigation. In addition, neuronal network activity and neuronal firing patterns have not been well studied in behaving tauopathy models. In this study, we first performed in vivo two-photon Ca2+ imaging in JNPL3 mice in their early stage of tauopathy at 6 months of age, compared to 12 month old mice and age-matched wild-type controls to evaluate neuronal functional deficits. At the animal level, frequency of neuronal Ca2+ transients decreased only in 6 month old tauopathy mice compared to controls, and only when animals were running on a treadmill. The amplitude of neuronal transients decreased in tauopathy mice compared to controls under resting and running conditions in both age groups. Total neuronal activity decreased only in 6 month old tauopathy mice compared to controls under resting and running conditions. Within either tauopathy or wild-type group, only total activity decreased in older wild-type animals. The tauopathy mice at different ages did not differ in neuronal Ca2+ transient frequency, amplitude or total activity. In summary, neuronal function did significantly attenuate at an early age in tauopathy mice compared to controls but interestingly did not deteriorate between 6 and 12 months of age. A more detailed populational analysis of the pattern of Ca2+ activity at the neuronal level in the 6 month old cohort confirmed neuronal hypoactivity in layer 2/3 of primary motor cortex, compared to wild-type controls, when animals were either resting or running on a treadmill. Despite reduced activity, neuronal Ca2+ profiles exhibited enhanced synchrony and dysregulated responses to running stimulus. Further ex vivo electrophysiological recordings revealed reduction of spontaneous excitatory synaptic transmission onto and in pyramidal neurons and enhanced excitability of inhibitory neurons in motor cortex, which were likely responsible for altered neuronal network activity in this region. Lastly, tau antibody treatment reduced pathological tau and gliosis partially restored the neuronal Ca2+ activity deficits but failed to rescue altered network changes. Taken together, substantial neuronal and network dysfunction occurred in the early stage of tauopathy that was partially alleviated with acute tau antibody treatment, which highlights the importance of functional assessment when evaluating the therapeutic potential of tau antibodies. HighlightsO_LILayer 2/3 motor cortical neurons exhibited hypofunction in awake and behaving mice at the early stage of tauopathy. C_LIO_LIAltered neuronal network activity disrupted local circuitry engagement in tauopathy mice during treadmill running. C_LIO_LILayer 2/3 motor cortical neurons in tauopathy mice exhibited enhanced neuronal excitability and altered excitatory synaptic transmissions. C_LIO_LIAcute tau antibody treatment reduced pathological tau and gliosis, and partially restored neuronal hypofunction profiles but not network dysfunction. C_LI

neuroscience↗

bioRxiv2024

A human forebrain organoid model reveals the essential function of GTF2IRD1-TTR-ERK axis for the neurodevelopmental deficits of Williams Syndrome

Williams Syndrome (WS; OMIM#194050) is a rare disorder, which is caused by the microdeletion of one copy of 25-27 genes, and WS patients display diverse neuronal deficits. Although remarkable progresses have been achieved, the mechanisms for these distinct deficits are still largely unknown. Here, we have shown that neural progenitor cells (NPCs) in WS forebrain organoids display abnormal proliferation and differentiation capabilities, and synapse formation. Genes with altered expression are related to neuronal development and neurogenesis. Single cell RNA-seq (scRNA-seq) data analysis revealed 13 clusters in healthy control and WS organoids. WS organoids show an aberrant generation of excitatory neurons. Mechanistically, the expression of transthyretin (TTR) are remarkably decreased in WS forebrain organoids. We have found that GTF2IRD1 encoded by one WS associated gene GTF2IRD1 binds to TTR promoter regions and regulates the expression of TTR. In addition, exogenous TTR can activate ERK signaling and rescue neurogenic deficits of WS forebrain organoids. Gtf2ird1 deficient mice display similar neurodevelopmental deficits as observed in WS organoids. Collectively, our study reveals critical function of GTF2IRD1 in regulating neurodevelopment of WS forebrain organoids and mice through regulating TTR-ERK pathway.

neuroscience↗

bioRxiv2024

A high-continuity and annotated reference genome of allotetraploid Siberian wildrye (Elymus sibiricus L., Poaceae: Triticeae)

Elymus sibiricus L. (Siberian wildrye, Es), a species belonging to the wheat tribe, is extensively employed as forage and for the reclamation of degraded grasslands within the Qinghai-Tibet Plateau (QTP). This study provides a high-quality reference genome assembly for the allotetraploid Es, which is composed of 14 pseudomolecules with the total genome size of 6.57 Gb. Our finding suggest that large-scale bursts of retrotransposons are critical for the genome expansion of Es. We discovered a translocation event between the Es4H and Es6H chromosomes with a low frequency of combination. Phylogenetic analyses of 90 Es accessions and 25 diploid accessions representing proposed ancestors from various habitats revealed the existence of four distinct populations. We further provided support for the hypothesis that the QTP is the center of origin and genetic diversity for Es. Collectively, our study offers valuable insights into the evolution of Es, as well as providing genomic resources for genetic enhancement in the Elymus genus and wheat tribe.

genomics↗

bioRxiv2024

Single-Domain Antibody-Based Protein Degrader for Synucleinopathies

Synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of -synuclein (-syn) in the brain, leading to motor and neuropsychiatric symptoms. Currently, there are no known cures for synucleinopathies, and treatments mainly focus on symptom management. In this study, we developed a single-domain antibody (sdAb)-based protein degrader with features designed to enhance proteasomal degradation of -syn. This sdAb derivative targets both -syn and Cereblon (CRBN), a substrate-receptor for the E3-ubiquitin ligase CRL4CRBN, and thereby induces -syn ubiquitination and proteasomal degradation. Our results indicate that this therapeutic candidate enhances proteasomal degradation of -syn, in addition to the endogenous lysosomal degradation machinery. By promoting proteasomal degradation of -syn, we improved clearance of -syn in primary culture and mouse models of synucleinopathy. These findings indicate that our sdAb-based protein degrader is a promising therapeutic candidate for synucleinopathies. Considering that only a small percentage of antibodies enter the brain, more potent sdAbs with greater brain entry than whole antibodies could enhance clinical benefits of antibody-based therapies.

neuroscience↗

bioRxiv2024

Defining cell type-specific immune responses in a mouse model of allergic contact dermatitis by single-cell transcriptomics

Allergic contact dermatitis (ACD), a prevalent inflammatory skin disease, is elicited upon repeated skin contact with protein-reactive chemicals through a complex and poorly characterized cellular network between immune cells and skin resident cells. Here, single-cell transcriptomic analysis of the murine hapten-elicited model of ACD reveals that upon elicitation of ACD, infiltrated CD4+ or CD8+ lymphocytes were primarily the IFN{gamma}-producing type 1 central memory phenotype. In contrast, type 2 cytokines (IL4 and IL13) were dominantly expressed by basophils, IL17A was primarily expressed by {delta}{gamma} T cells, and IL1{beta} was identified as the primary cytokine expressed by activated neutrophils/monocytes and macrophages. Furthermore, analysis of skin resident cells identified a sub-cluster of dermal fibroblasts with preadipocyte signature as a prominent target for IFN{gamma}+ lymphocytes and dermal source for key T cell chemokines CXCL9/10. IFN{gamma} treatment shifted dermal fibroblasts from collagen-producing to CXCL9/10-producing, which promoted T cell polarization toward the type-1 phenotype through a CXCR3-dependent mechanism. Furthermore, targeted deletion of Ifngr1 in dermal fibroblasts in mice reduced Cxcl9/10 expression, dermal infiltration of CD8+ T cell, and alleviated ACD inflammation in mice. Finally, we showed that IFN{gamma}+ CD8+ T cells and CXCL10-producing dermal fibroblasts co-enriched in the dermis of human ACD skin. Together, our results define the cell type-specific immune responses in ACD, and recognize an indispensable role of dermal fibroblasts in shaping the development of type-1 skin inflammation through the IFNGR-CXCR3 signaling circuit during ACD pathogenesis.

immunology↗