About

Gaetan Barbet is an Assistant Professor in the Department of Pediatrics at Rutgers University. His major research interests include immunology, microbiome, and signaling. His laboratory studies the biology of mononuclear phagocytes such as monocytes, dendritic cells, and macrophages, focusing on calcium homeostasis and its role in environmental sensing within these cells. The research investigates calcium signaling in the context of pathogen recognition and cell death responses. Additionally, his work explores how mononuclear phagocytes at mucosal surfaces, such as the lungs and intestines, orchestrate immune responses to promote either efficient adaptive immunity, including antibody production, or tissue repair.

Research topics

• Biology
• Cell biology
• Immunology
• Andrology
• Anatomy
• Genetics
• Medicine
• Pathology
• Biochemistry
• Internal medicine

Selected publications

• Characterization of an IgA-eliciting mechanism to improve oral vaccine 2252

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Current parenteral vaccines effectively generate systemic immunity through IgG antibodies but are not efficient in producing a robust mucosal immunity, mediated by IgA antibodies, which are essential for preventing infections by mucosal pathogens. Here, we explore how key inflammatory molecules, TRIF and IL1R1, inhibit IgA production in the murine intestine. In absence of infection, we observed that Trif- and Il1r1-deficient mice harbored a higher percentage of IgA-bound bacteria and free IgAs in stools compared to control mice. This boost in IgA correlates with the enrichment in the Peyer’s patches of follicular helper T cells, which are critical for germinal center formation. Furthermore, increased IgA production in absence of TRIF and IL1R1 correlates with elevated retinoic acid metabolism in Peyer’s patches, aligning with existing knowledge regarding its role in IgA production. We also identified an uncharacterized bacterium from the Muribaculaceae family as a target of these intestinal IgAs, suggesting its potential as an antigen vector for intestinal immunizations. Additionally, oral immunization with protein-based vaccines elicited heightened IgA responses in the intestine of Trif- and Il1r1-deficient mice compared to control mice. Overall, our findings highlight the specificity of the mechanisms, within the Peyer’s patches, leading to mucosal immunity, paving the way for more targeted and effective mucosal and oral vaccines. Funding Sources Moderna Project # 835603 RWJF Grant Project # 826399 Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• Distinct mural cells and fibroblasts promote pathogenic plasma cell accumulation in idiopathic pulmonary fibrosis

  European Respiratory Journal · 2025-02-20 · 15 citations

  article

  BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by significant but poorly understood immune and antibody responses. This study examines the spatial transcriptomes and microenvironmental niches of antibody-producing plasma cells and tertiary lymphoid structures in IPF lungs, and the molecular pathways influencing antibody accumulation and pulmonary fibrosis. METHODS: Explant lung tissues from IPF patients and control normal lungs were used for spatial transcriptome assays and validating RNAscope and immunofluorescence assays. Fibroblasts derived from IPF and control lungs were examined for their ability to attract plasma cells. Neutralising antibodies were administered to investigate molecules affecting pulmonary plasma cell accumulation and fibrosis in bleomycin-treated mice. RESULTS: Human IPF lungs exhibited a remarkably widespread distribution of plasma cells and local antibodies in the fibrotic regions, disseminating from plasma cell-generating tertiary lymphoid structures. Novel mural cells wrapped the vessels in tertiary lymphoid structure regions, expressing C-C motif chemokine receptor 7 (CCR7) ligands that attracted T-cells into tertiary lymphoid structures to promote plasma cell generation. Distinct IPF-associated fibroblasts further secreted C-X-C motif chemokine ligand 12 (CXCL12), providing an extramedullary niche to foster the dissemination and accumulation of plasma cells in the fibrotic regions. Neutralisation of CCR7 ligands or CXCL12 reduced plasma cell and local antibody accumulation in the lungs of bleomycin-treated mice, leading to reduced transforming growth factor β concentrations and alleviated pulmonary fibrosis. CONCLUSIONS: Plasma cells and local antibodies are widely distributed in the fibrotic regions of IPF lungs. Distinct subsets of IPF-associated mural cells and fibroblasts promote pathological plasma cell and antibody accumulation. These findings have potential implications for strategies aimed at targeting immune and antibody responses to combat IPF.

  PublisherDOI

• A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis

  Nature Immunology · 2025-01-01 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Bacterial Induced Calcium Dynamics in Dendritic Cells In Vivo 2225

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Dendritic cells (DCs) are sentinels that orchestrate immune responses to infections, cancer, and tissue damage. DCs play a crucial role bridging the innate and adaptive immune systems, eliciting tailored adaptive immune responses. Manipulation of DCs is critical for vaccination, DC-based immunotherapies have been tested in clinical trials as anti-cancer therapeutics and for treatment of infectious diseases. Calcium, a ubiquitous secondary messenger, regulates many critical effector functions of DCs like phagocytosis, maturation, migration, and cytokine production. However, calcium’s dynamics in DCs remains poorly understood. To decipher calcium signals induced by bacterial stimuli in DCs intravitally, we generated CD11c-Salsa6f reporter mice that express the fluorescent protein (FP) construct tdTomato fused to GCaMP6f in CD11c expressing cells. Expression of tdTomato, a red FP, highlights cell shape, and GCaMP6f, which fluoresces green upon calcium binding, visualizes intracellular calcium levels. Using intravital microscopy on mice intravenously injected with bacteria, we discovered oscillatory calcium signaling in splenic that are specific to the type and viability of bacteria. Additionally, the intensity of calcium signal correlated with reactive oxygen species production. This intravital study on splenic DCs underscores the crucial role of calcium homeostasis in response to bacteria, and how it affects downstream pathways crucial for control of bacterial infections. Funding Sources Krieger Klein Alzheimer’s Research Center Pilot Award in collaboration with Dr. Max Tischfield, “Piezo1 restoration of glymphatic waste clearance in aging and Alzheimer’s disease” Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)

  PublisherOA PDFDOI

• Activation of PIEZO1 Evokes Calcium Flux and Promotes Human Airway Smooth Muscle Cell Relaxation

  2024-04-30

  article
  PublisherDOI

• Large Deviations of Piecewise-Deterministic-Markov-Processes with Application to Stochastic Calcium Waves

  arXiv (Cornell University) · 2024-06-18

  preprintOpen access1st authorCorresponding

  We prove a Large Deviation Principle for Piecewise Deterministic Markov Processes (PDMPs). This is an asymptotic estimate for the probability of a trajectory in the large size limit. Explicit Euler-Lagrange equations are determined for computing optimal first-hitting-time trajectories. The results are applied to a model of stochastic calcium dynamics. It is widely conjectured that the mechanism of calcium puff generation is a multiscale process: with microscopic stochastic fluctuations in the opening and closing of individual channels generating cell-wide waves via the diffusion of calcium and other signaling molecules. We model this system as a PDMP, with $N \gg 1$ stochastic calcium channels that are coupled via the ambient calcium concentration. We employ the Large Deviations theory to estimate the probability of cell-wide calcium waves being produced through microscopic stochasticity.

  PublisherOA PDFDOI

• TGFB1 induces fetal reprogramming and enhances intestinal regeneration

  Cell stem cell · 2023 · 95 citations

  • Biology
  • Cell biology
  • Andrology
  PublisherOA PDFDOI

• Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice

  Journal of Clinical Investigation · 2023 · 43 citations

  • Medicine
  • Pathology
  • Anatomy

  Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these processes are affected by craniofacial disorders such as craniosynostosis are poorly understood. We report that raised intracranial pressure and diminished CSF flow in craniosynostosis mouse models associate with pathological changes to meningeal lymphatic vessels that affect their sprouting, expansion, and long-term maintenance. We also show that craniosynostosis affects CSF circulatory pathways and perfusion into the brain. Further, craniosynostosis exacerbates amyloid pathology and plaque buildup in Twist1+/-:5xFAD transgenic Alzheimer's disease models. Treating craniosynostosis mice with Yoda1, a small molecule agonist for Piezo1, reduces intracranial pressure and improves CSF flow, in addition to restoring meningeal lymphangiogenesis, drainage to the deep cervical lymph nodes, and brain-CSF perfusion. Leveraging these findings, we show that Yoda1 treatments in aged mice with reduced CSF flow and turnover improve lymphatic networks, drainage, and brain-CSF perfusion. Our results suggest that CSF provides mechanical force to facilitate meningeal lymphatic growth and maintenance. Additionally, applying Yoda1 agonist in conditions with raised intracranial pressure and/or diminished CSF flow, as seen in craniosynostosis or with ageing, is a possible therapeutic option to help restore meningeal lymphatic networks and brain-CSF perfusion.

  PublisherOA PDFDOI

• Characterization of Calcium signals and oscillations in dendritic cells <i>in vivo</i> in response to pathogens

  The Journal of Immunology · 2023-05-01

  articleOpen accessSenior author

  Abstract Dendritic cells (DCs) are disseminated throughout organisms and serve as sentinels, organizing immune responses to infection, tissue damage, and cancer. DCs play a crucial role bridging innate and adaptive immune systems and elicit a tailored adaptive immune response to the types of threats they encounter. Manipulation of DCs is critical for vaccination, and DC-based immunotherapies have been tested in clinical trials as anti-cancer therapeutics and for treatment of infectious diseases. Calcium, a ubiquitous secondary messenger, regulates many critical effector functions of DCs like phagocytosis, maturation, migration, and cytokine production. However, regulation and mobilization of calcium in DCs remains poorly understood. Using microscopy, our preliminary experiments unveiled for the first time an oscillatory calcium signal in DCs in response to whole bacteria; our in vitro studies show that oscillatory calcium signaling patterns are specific to the type of bacteria. To decipher calcium signals induced by bacterial stimuli in DCs intravitally, we generated CD11c-Salsa6f reporter mice that express the fluorescent protein (FP) construct tdTomato fused to GCaMP6f in CD11c expressing cells. Hence, expression of TdTomato, a red FP, highlights cell shape, and GCaMP6f, which fluoresces green upon calcium binding, visualizes intracellular calcium levels. We are using CD11c-Salsa6f mice to observe calcium signals in DCs in the periphery and in secondary lymphoid organs using two photon microscopy. This model, perfectly suited for intravital two photon microscopy, allows us to unveil bacteria-specific calcium signals in DCs in in their natural microenvironment. Supported by a grant from the NIH (1T32GM139804-01)

  PublisherOA PDFDOI

• Negative regulation of intestinal IgA by inflammatory cues in absence of infection

  The Journal of Immunology · 2023-05-01

  articleOpen accessSenior author

  Abstract Pathogen-specific IgA elicited at mucosal site is associated with a better immune protection upon vaccination. Although some effective mucosal vaccines are available and approved, the majority of current vaccines are administered intramuscularly or subcutaneously and were developed irrespectively of a particular site of infection. Vaccine adjuvants are selected in their capacity to elicit a strong inflammatory response. However, few studies show the effectiveness of FDA-approved adjuvants to mucosal vaccines. Here, we unveil the role of inflammatory pathways in their negative regulation of IgA production in murine intestines. We are currently studying and identifying the molecular and cellular pathways involved in the production of protective IgA antibodies in the intestines in absence of particular inflammatory cues. Indeed, in absence of some inflammatory signals, we observed an increase of free IgAs and IgA-bound bacteria in the intestines of mice in steady state. IgA levels were normal in the serum and the concentration of IgG antibodies were also normal in both the intestines and serum suggesting a skewed toward IgAs restricted to the intestines. Furthermore, we could show that this IgA production is for the most part T-dependent and involves the formation of germinal centers localized in the Peyer’s Patches. We are now developing vaccine models to elicit potent IgA-mediated protection in the aim to use these finding at our advantage to promote pathogen-specific intestinal responses through new designs of mucosal vaccines. We believe that developing mucosal vaccines that elicit a protective immunity through natural routes of infection hold the promise to act better, faster and safer against worldwide pathogenic threat. RWJF Grant Project # 826399 Moderna Research Fellowship

  PublisherOA PDFDOI

Frequent coauthors

• Pierre Launay

  Centre National de la Recherche Scientifique

  26 shared

• François Vrtovsnik

  Université Claude Bernard Lyon 1

  22 shared

• Marie Demion

  Hôpital Arnaud de Villeneuve

  18 shared

• Nicolas Serafini

  Université Paris Cité

  18 shared

• Hervé Souchet

  16 shared

• Tarik Attout

  Inserm

  16 shared

• Michelle Arcos‐Fajardo

  University of Bari Aldo Moro

  16 shared

• Albert Dahdah

  University of Oklahoma Health Sciences Center

  16 shared

Education

• Ph.D.

  Université Paris Diderot

  2009