Biology subjects

yang, z.

Publications and source records attributed to yang, z..

6 recordsLinked to original sources

bioRxiv2026

Tissue retention of dendritic cells drives age-associated protective tolerogenic lymphoid structures

Ectopic lymphoid structures are typically associated with chronic tissue inflammation in autoimmunity and cancer, where they can amplify local immune responses. Similar structures arise spontaneously with age, yet their origin and function remain unclear. Here we identify tissue retention of mature migratory conventional dendritic cells (cDCs) as a driver of age-associated lymphoid organization. Mature cDCs accumulated within lymphoid structures in aged human and mouse tissues. We demonstrate that impaired cDC egress or pharmacological cDC expansion induced de novo structures in mice across multiple otherwise homeostatic organs without associated pathology. Strikingly, senescence-associated tissue cues, which promoted a distinct cDC maturation state, were required for lymphoid niche initiation. Unlike inflammatory structures described in disease, these cDC-driven structures preferentially accumulated tissue-adapted regulatory T cells and protected against inflammatory injury, revealing a previously unrecognized regulatory dimension of age-associated lymphoid organization.

immunology↗

bioRxiv2026

Smallpox Vaccine Elicits CD8+ T Cell Immunity Persisting Over Four Decades with Cross-Recognition of Monkeypox Virus

Monkeypox, caused by MPXV, has become a global public health concern; however, the T-cell immunity against MPXV following smallpox vaccination remains unclear. In this study, we screened the immunogenicity of 21 predicted MPXV epitopes and compared immune responses between young and elderly groups. Two immunogenic CD8 T-cell epitopes, M15 and M17, were identified, both of which effectively stimulated specific immune responses, with significantly stronger responses observed in the young group. Notably, this study provides the first evidence that smallpox vaccination induces CD8 T-cell immunity that cross-recognizes the MPXV epitopes M15 and M17 and remains detectable for more than four decades after vaccination, as demonstrated in vaccinated individuals aged 53-75. These findings provide experimental evidence for understanding the cross-protective mechanisms of the smallpox vaccine and informing monkeypox vaccine development.

immunology↗

bioRxiv2025

16S rRNA Survey Reveals the Potential of Oral Microbiota in Distinguishing Patients with Chronic Heart Failure from Healthy Controls

BackgroundOral microbiota can reflect physiological functions and pathological conditions in human body. Patients with chronic heart failure (CHF) exhibit distinct oral health status compared to healthy controls (HCs), which is attributed to the differences in dominant microbial communities present in the oral cavity. Up to date, there are few studies examined the association between CHF and dominant oral microbiota. To fill in this research gap, this study aimed to investigate the differences of oral microbiota between CHF patients and HCs, to identify valuable novel biomarkers for CHF. MethodsChronic heart failure patients and healthy volunteers were recruited. Oral microbiota samples were then collected using oral swabs, and 16S rRNA sequencing was employed to analyze the microbiota. Statistical analysis was conducted to identify key bacteria at multiple taxonomic levels in the oral microbiota samples from both the CHF patient and healthy control groups, with a focus on core genera to identify potential biomarkers and evaluate their diagnostic efficacy. ResultsThere were 60 CHF patients and 30 HCs were recruited, with 42 CHF patients with New York Heart Association (NYHA) functional class II-IV and 28 HCs were included in the final analysis. The alpha diversity was higher in HCs, while beta diversity was higher in CHF patients. The CHF patients showed significant differences from HCs at five gene (phylum, class, order, family and genus) levels by analyzing the relative richness of microbiota at different taxomal levels. Altogether 14 microbes could distinguish CHF patients from HCs, i.e., Abiotrophia, Butyrivibrio, Lactobacillus, Capnocytophaga and Neisseria which are more abundant in CHF patients, and Actinomyces, Anaerovorax, Eubacterium, Kingella, Mogibacterium, Peptococcus, Peptostreptococcus, Solobacterium and TM7_genus_incertae_sedis which are more abundant in HCs. Furthermore, the AUC of their combined diagnosis was 83.7% (95% confidential interval 74.1%-93.3%), which have high reliability for the diagnostic significance. In accordance to Spearmans correlation, Eubacterium, Solobacterium and Rhizobium were core genera and the abundance of Eubacterium and Solobacterium exhibited downward trends as NYHA class increases. ConclusionThis study revealed the dysbiosis of the oral microbiota in CHF patients and identified potential biomarkers for CHF diagnosis and management. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/669863v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@d60f6eorg.highwire.dtl.DTLVardef@18f17ceorg.highwire.dtl.DTLVardef@163f0daorg.highwire.dtl.DTLVardef@599bcd_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Early-life Microbiome-Derived HCA Enhances Type 3 Immunity via FXR-dependent m6A RNA methylation

The gut microbiome plays a crucial role in the development of intestinal immunity during early life, but the underlying mechanisms remain largely unknown. Here, we found oxygen consumption in neonatal rats by S. boulardii accelerated the colonization of the microbiome and the development of type 3 immunity, which protected against S. typhimurium. Microbiome maturation increased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and elevated the levels of Hyocholic acid (HCA). HCA promotes the development of {gamma}{delta}T and type 3 innate lymphoid cell (ILC3) by sustaining the stability of Rorc mRNA via the FXR-WTAP- N6-methyl-adenosine (m6A) axis. L. reuteri, a bacterium encoding BSH, was enriched by oxygen consumption in the intestine and promoted intestinal type 3 immunity. However, inhibition of BSH blocks the L. reuteri-induced development of intestinal type 3 immunity. These results reveal the role of microbiome-derived HCA in the regulation of intestinal type 3 immunity during early life.

microbiology↗

bioRxiv2023

Force sensing GPR133 is essential for normal balance and modulates vestibular hair cell membrane excitability via Gi signaling and CNGA3 coupling

The maintenance of normal balance sensing is a fundamental prerequisite for virtually every activity of daily life. As one set most important balance information collectors, vestibular hair cells convert mechanical stimuli from head movement into electrical signals through a mechanoelectrical transduction (MET) process. The molecular mechanism underlying equilibrioception and MET in vestibular hair cells is not well understood but is generally believed to be mediated by ion channels. However, whether these procedures are also mediated by other receptors, such as GPCRs, which are known to govern light, odorant and taste sensing, is not known. Here, by screening the expression of force-sensitive adhesion GPCRs in vestibular hair cells and phenotype profiling in animal models, we identified that a seven-transmembrane receptor, GPR133, was able to sense force in utricle hair cells and was required for maintenance of normal equilibrioception. Notably, GPR133 converted mechanical stimuli into changes in intracellular cAMP levels through Gi engagement and then modulated plasma membrane excitability and mediated MET by coupling to CNGA3 activity changes in approximately 30% of GPR133-expressing utricle hair cells. GPR133-mediated MET and its coupling with CNGA3 were recapitulated by an in vitro reconstitution system. Further chemical labeling, mass spectrometry and cryo-EM analysis provided potential structural information on force-induced GPR133 activation and Gi3 engagement. Collectively, our findings reveal the essential role of GPR133 in the maintenance of normal equilibrioception and suggest that GPCR family members can participate in the MET process in utricle hair cells through modulation of intracellular second messenger levels and ion channel coupling.

physiology↗

bioRxiv2023

Force sensation by a Gs-coupled adhesion GPCR mediates equilibrioception by increasing vestibular hair cell membrane excitability and CNGA3 coupling

AbstractEquilibrioception is essential for the perception and navigation of mammals in the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells plays a critical role in positional and motional perception. Here, we identified that the G protein-coupled receptor LPHN2/ADGRL2, which is expressed in the apical membrane of utricular hair cells, is required for maintenance of normal balance. Hair cell-specific Lphn2 deficiency in mice impaired both balance behaviors and MET responses. Functional analyses using Pou4f3-CreER+/-; Lphn2fl/fl mice and LPHN2-specific inhibitors revealed that LPHN2 regulated the tip link-independent MET current at the apical surface of the utricular hair cell by converting force stimuli into transmembrane channel-like protein 1 (TMC1) activity. Force sensation by LPHN2 also induced glutamate release and calcium signaling in utricular hair cells. Reintroduction of LPHN2 into the hair cells of Lphn2-deficient mice restored the vestibular functions and MET responses. Our data suggest an indispensable role for a mechanosensitive GPCR in equilibrioception.

physiology↗