Biology subjects

Ping, S.

Publications and source records attributed to Ping, S..

3 recordsLinked to original sources

bioRxiv2025

Epithelial FOXP3 Drives Pancreatic Fibrosis through O-glycosylated IL-6

BACKGROUND & AIMSThe transcription factor FOXP3, known for specifying regulatory T cell fate, is unexpectedly expressed in the epithelium of precancerous pancreatic lesions. Here we investigate its non-immune role in initiating pancreatic fibrosis, a process driving therapeutic resistance and organ failure in pancreatic ductal adenocarcinoma (PDAC) with unknown origins in early neoplasia. METHODSUsing human tissues and genetically engineered mouse models, we analysed FOXP3 expression in premalignant lesions. We employed epithelial-specific FOXP3 knockout and knock-in strategies to determine its functional impact on fibrogenesis and neoplasia progression. Mechanistic studies included chromatin immunoprecipitation, glycomic analyses, and signalling assays. RESULTSFOXP3 was consistently expressed in the epithelial compartment of human and murine precancerous pancreas. Epithelial-specific deletion of FOXP3 attenuated pancreatic fibrosis and delayed neoplasia, whereas its knock-in induced spontaneous stromal activation and accelerated PanIN progression. Mechanistically, epithelial FOXP3 directly transactivated the glycosyltransferase GALNT1. GALNT1, in turn, mediated O-glycosylation of interleukin (IL)-6, which was essential for its rapid secretion. CONCLUSIONSOur study establishes epithelial-derived FOXP3 as a master regulator of early pancreatic fibrocarcinogenesis. It drives a glycosylation-dependent amplification loop for IL-6 signalling, orchestrating sustained stromal activation. This pathway represents a promising target for intercepting pancreatic fibrosis and carcinogenesis at its origin.

cancer biology↗

bioRxiv2025

The magnitude and durability of neutralizing antibody responses to human papillomavirus vaccine do not depend on DNA sensing pathways

How human papillomavirus (HPV) vaccines elicit robust and enduring neutralizing antibody (nAb) responses is unknown, yet such information is valuable to vaccinology. In addition to the major capsid protein, L1, the 4-valent HPV vaccine reportedly also contains recombinant L1 DNA. Nucleic acids in vaccines can enhance antibody responses, but whether L1 DNA enhances HPV vaccine antibody responses is understudied. We tested whether 9-valent HPV (9vHPV) vaccine lots contained L1 DNA and if peak or long-term 9vHPV vaccine-elicited nAb responses were dependent on DNA sensors TLR9, AIM2, or cGAS, or STING or MyD88, the adaptors for cGAS and TLR9, respectively. To quantify L1 DNA, we extracted total nucleic acid per 9vHPV dose and applied singleplex quantitative PCR to amplify HPV6/11/16/18/31/33/45/52/58 L1 sequences. Wildtype mice (wt; C57BL/6J) or mice deficient in DNA sensing pathways (TLR9-/-, AIM2-/-, cGAS-/-, STINGgt/gt, MyD88-/-) were administered 9vHPV vaccine or equivalent adjuvant only at 0, 4, and 12 weeks. We measured serum HPV16 and HPV18 nAb titers at 16, 26, 40, and 53-56 weeks and HPV16- and HPV18-specific bone marrow plasma cell responses at 53-56 weeks. We detected 5-44 and 104-351 copies of HPV6 and HPV18 L1 DNA per 9vHPV vaccine dose, but no other types (n=3 lots). We found no consistent difference in geometric mean nAb titers between mice strains that received 9vHPV at any time point tested or in median HPV16- or HPV18-specific plasma cell frequencies. Thus, we conclude the magnitude and durability of nAb responses to 9vHPV vaccination do not depend on DNA sensing pathways.

immunology↗

bioRxiv2023

Stem cell factor and granulocyte colony-stimulating factor promote remyelination in the chronic phase of severe traumatic brain injury

Severe traumatic brain injury (TBI) causes long-term disability and death in young adults. White matter is vulnerable to TBI damage. Demyelination is a major pathological change of white matter injury after TBI. Demyelination which is characterized by myelin sheath disruption and oligodendrocyte cell death leads to long-term neurological function deficits. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) treatments have shown neuroprotective and neurorestorative effects in the subacute and chronic phases of experimental TBI. Our previous study has revealed that combined SCF and G-CSF treatment (SCF+G-CSF) enhances myelin repair in the chronic phase of TBI. However, the long-term effect and mechanism of SCF+G-CSF-enhanced myelin repair remain unclear. In this study, we uncovered persistent and progressive myelin loss in the chronic phase of severe TBI. SCF+G-CSF treatment in the chronic phase of severe TBI enhanced remyelination in the ipsilateral external capsule and striatum. The SCF+G-CSF-enhanced myelin repair is positively correlated with the proliferation of oligodendrocyte progenitor cells in the subventricular zone. These findings reveal the therapeutic potential of SCF+G-CSF in myelin repair in the chronic phase of severe TBI and shed light on the mechanism underlying SCF+G-CSF-enhanced remyelination in chronic TBI.

neuroscience↗