Biology subjects

Xu, J. Z.

Publications and source records attributed to Xu, J. Z..

6 recordsLinked to original sources

bioRxiv2026

Neonatal regulatory T cells promote alveologenesis by restraining neutrophil-mediated inflammation

Alveologenesis during early postnatal life requires tight coordination between epithelial differentiation and immune regulation, yet how immune cells contribute to this process remains unclear. Regulatory T cells (Tregs) are established mediators of immune homeostasis and tissue repair in adult lung injury, but their role in lung development is unknown. Here, we identify a transient wave of highly proliferative, activated Tregs that accumulates in the neonatal lung during an early postnatal window. Using inducible Treg ablation, we show that loss of this neonatal Treg population disrupts alveologenesis, resulting in enlarged airspaces, and persistent structural abnormalities later in life. Treg depletion also induces interferon-associated inflammatory programmes, promotes neutrophil accumulation, and is accompanied by a sustained imbalance in alveolar epithelial populations. Notably, neutrophil depletion partially rescues both epithelial composition and alveolar structure, identifying neutrophils as key downstream effectors of Treg-mediated regulation. Together, these findings show that neonatal Tregs are required for normal alveologenesis by restraining neutrophil-driven inflammation and preserving epithelial balance. Our study reveals a previously unappreciated role for immune regulation in lung organogenesis.

immunology↗

bioRxiv2024

Jagged-1+ Tregs Mediate Lymphatic Remodeling in Tumour-Draining Lymph Nodes

The tumour-draining lymph nodes (tdLNs) are crucial sites for early immune surveillance of tumours. During tumour development, tdLNs undergo significant stromal remodelling that impacts lymph node (LN) architecture. The reconstruction of tdLNs is dependent on the crosstalk between regulatory T cells (Tregs) and resident stromal cells. The Notch ligand Jagged1 (Jag1), highly expressed in skin Tregs, is critical for facilitating stem cell-mediated tissue regeneration. However, the role of Jag1pos Tregs in mediating the activity of tdLN-resident immune cells and stromal cells remains unexplored. Here, we used the B16-F10 tumour model to assess the role of Jag1pos Tregs during tdLN development. During tumor progression, late-stage tdLN Tregs expressed higher levels of Jag1 than early-stage tdLNs. Conditional deletion of Jag1 in Tregs markedly restrained tdLN expansion, without influencing effector T cell abundance or activation profile. Transcriptomic analysis of tdLNs revealed downregulation of lymphatic endothelial cell (LEC)-related markers in mice with Treg-specific Jag1 ablation. Disruption of lymphatic networks in the tdLN was further confirmed by flow cytometric profiling and histological analysis. In vivo permeability assessment by FITC-dextran demonstrated perturbed lymphatic drainage, likely due to suppressed LN lymphangiogenesis. Finally, we identify the presence of Jag1pos Tregs in tdLNs of human melanoma patients. Overall, our results highlight that crosstalk between Jag1pos Tregs and LECs is required for lymphatic sinus expansion, which is critical for the formation of the tdLN niche during melanoma progression.

immunology↗

bioRxiv2024

Jagged-1+ Skin Tregs Modulate the Innate Immune Response to Wound Healing

Skin-resident regulatory T cells (Tregs) play an irreplaceable role in orchestrating cutaneous immune homeostasis and repair, including the promotion of hair regeneration via the Notch signaling ligand Jagged-1 (Jag1). While skin Tregs are indispensable for facilitating tissue repair post-wounding, it remains unknown if Jag1-expressing skin Tregs impact wound healing. Using a tamoxifen inducible Foxp3creERT2Jag1fl/fl model, we show that loss of functional Jag1 in Tregs significantly delays the rate of full-thickness wound closure. Unlike in hair regeneration, skin Tregs do not utilize Jag1 to impact epithelial stem cells during wound healing. Instead, mice with Treg-specific Jag1 ablation exhibit a significant reduction in Ly6G+ neutrophil accumulation at the wound site. However, during both homeostasis and wound healing, the loss of Jag1 in Tregs does not impact the overall abundance or activation profile of immune cell targets in the skin, such as CD4+ and CD8+ T cells, or pro-inflammatory macrophages. This collectively suggests that skin Tregs may utilize Jag1-Notch signalling to co-ordinate innate cell recruitment under conditions of injury but not homeostasis. Overall, our study demonstrates the importance of Jag1 expression in Tregs to facilitate adequate wound repair in the skin.

immunology↗

bioRxiv2023

Rapid and Highly Sensitive Detection of Fentanyl and its Analogs by a Novel Chemiluminescence Immunoassay

A highly sensitive immunoassay with sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When applied to unaltered clinical human urine samples, the assay has sub-picogram limit of detection for fentanyl, with results fully concordant with gold standard liquid chromatography-mass spectrometry. When applied to environmental samples, the assay can detect as low as 0.25 pg fentanyl per inch2 environment surface. Assay turn-around-time is less than 1 hour, with inexpensive equipment needed and potential for high throughput automation or in-field screening. This novel assay has broad potential applications in clinical, environmental, occupational and forensic scenarios by detecting trace amount of fentanyl and its analogs to keep frontline workers safe.

pharmacology and toxicology↗

bioRxiv2023

Early life regulatory T cells modulate PPARγ-dependent skin pigmentation

The maintenance of adult tissue homeostasis is dependent on the functional cross-talk between stem cells (SCs) and tissue-resident immune cells. This reciprocal relationship is also essential for tissue organogenesis during early life. The skin harbors a relatively large population of Regulatory T cells (Tregs) that accumulate within the first two weeks after birth. A functional role for early skin seeding Tregs (ETregs) during the first week of life is currently unexplored. Here, we show that skin Tregs are detected early as postnatal day 3 (P3) where they localize to hair follicle (HF) structures and enter a dynamic flux of activation marker expression. Punctual ETreg depletion from P6-P8, but not later, results in defective HF melanocyte SC (MeSC) mediated skin pigmentation in juvenile life. Transcriptomic analysis of the whole skin on P9 exhibited immediate and pronounced changes in MeSC markers and perturbation of Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) target genes in the HF. Accordingly, punctual ETreg depletion combined with short-term PPAR{gamma} agonization restored skin pigmentation. Single cell profiling of P9 skin revealed that PPAR{gamma} signalling activity is preferentially diminished in the HF epithelium upon loss of ETregs. Finally, we explored changes in the single cell transcriptome of the human tissue disorder, vitiligo, characterized by a lack of melanin and consequent skin depigmentation. These analyses showed that the HF cells from lesional vitiligo skin exhibited a significant downregulation in PPAR{gamma} pathway activation, relative to heathy controls. Overall, ETregs in neonatal skin are critical for sustaining HF PPAR{gamma} signaling, which is vital for facilitating MeSC mediated skin pigmentation during postnatal development. One Sentence SummaryPPAR{gamma} pathway functions downstream of neonatal Tregs to regulate melanocyte stem cell function.

immunology↗

bioRxiv2019

TLR3 Deficiency Leads to Altered Immune Responses to Chlamydia trachomatis Infection in Human Oviduct Epithelial Cells

Reproductive tract pathology caused by Chlamydia trachomatis infection is an important global cause of human infertility. To better understand the mechanisms associated with Chlamydia-induced genital tract pathogenesis in humans, we used CRISPR genome editing to disrupt TLR3 function in the human oviduct epithelial (hOE) cell-line OE-E6/E7, in order to investigate the possible role(s) of TLR3 signaling in the immune response to Chlamydia. Disruption of TLR3 function in these cells significantly diminished the Chlamydia-induced synthesis of several inflammation biomarkers including IFN-{beta}, IL-6, IL-6Ra, sIL-6R{beta} (gp130), IL-8, IL-20, IL-26, IL-34, sTNF-R1, TNFSF13B, MMP-1, MMP-2, and MMP-3. In contrast, the Chlamydia-induced synthesis of CCL-5, IL-29 (IFN{lambda}1) and IL-28A (IFN{lambda}2) were significantly increased in the TLR3-deficient hOE cells when compared to their wild-type counterparts. Our results propose a role for TLR3 signaling in limiting the genital tract fibrosis, scarring, and chronic inflammation often associated with human chlamydial disease. Interestingly, we saw that Chlamydia infection induced the production of biomarkers associated with persistence, tumor metastasis, and autoimmunity such as soluble CD163 (sCD163), chitinase-3-like protein 1, osteopontin, and pentraxin-3 in the hOE cells; however, their expression levels were significantly dysregulated in the TLR3-deficient hOE cells. Finally, we demonstrate using the hOE cells that TLR3 deficiency resulted in an increased amount of chlamydial LPS within the Chlamydia inclusion, which is suggestive that TLR3 deficiency leads to enhanced chlamydial replication and possibly increased genital tract pathogenesis during human infection.\n\nAbbreviationshOE, human OE-E6/E7 cells; TLR3 KO, TLR3 knockout cell line; poly (I:C), Polyinosinic-polycytidylic acid sodium salt.

microbiology↗