Biology subjects

Fauny, J.-D.

Publications and source records attributed to Fauny, J.-D..

3 recordsLinked to original sources

bioRxiv2026

Influenza Virus Infection of an Immunocompetent Organotypic Model of the Human Respiratory Mucosa

Respiratory infectious diseases are among the leading causes of global morbidity and mortality and remain a major public health concern. Progress in understanding early host-pathogen interactions has been hampered by the limited physiological relevance of existing experimental systems. Different models mimicking the human respiratory epithelium have been developed to study viral infections in vitro, such as tridimensional (3D) tissue models and organoids. However, many lack key features of human tissue architecture, particularly the lamina propria or immune cells. To address these limitations, we established an immunocompetent 3D model of the human respiratory mucosa by combining nasal epithelial cells isolated from nasal brushings, fibroblasts from mid-turbinate nasal biopsies, and macrophages derived from blood monocytes. These cells were sequentially seeded into collagen-chitosan scaffolds, resulting in a reconstructed respiratory mucosa closely resembling the in vivo nasal tissues. To further confirm the physiological relevance of the model, we infected it with influenza A virus. The mucosa model supported viral replication in the epithelium and consequently showed increased secretion of inflammatory cytokines and upregulation of type I interferon related genes, enabling the monitoring of early antiviral innate immune responses in a physiologically relevant context.

bioengineering↗

bioRxiv2024

Targeting B and T lymphocyte attenuator regulates lupus disease development in NZB/W mice

B and T Lymphocyte Attenuator (BTLA) is a co-inhibitory receptor expressed by most immune cells, playing a role in negatively regulating immune responses. Studies in MRL/lpr lupus mice deficient for BTLA, indicate that BTLA has a protective role in lupus. We have previously shown an altered BTLA expression by regulatory T cells and an impaired capacity of BTLA to inhibit CD4+ T cell activation in lupus patients. In this study, we thoroughly analyzed BTLA expression and function in the NZB/W lupus-mouse model. We found that diseased NZB/W mice exhibit a BTLA expression and function pattern similar to that observed in lupus patients, emphasizing the importance of this mouse model in evaluating the therapeutic potential of targeting BTLA. Administration of a monoclonal anti-BTLA antibody (clone 6F7, which displays agonist properties ex vivo) into pre-diseased NZB/W mice resulted in a delayed onset of proteinuria, limited kidney damages and an increased survival rate compared to isotype-treated mice. This beneficial effect was associated with a decrease in circulating B cell frequency and required continuous exposure to the antibody. Regarding its mode of action, we demonstrated that the 6F7 antibody is not a depleting antibody and does not block HVEM binding to BTLA, but instead induces BTLA down modulation, leading to a selective reduction of follicular B cell numbers, and exhibits in vivo agonist activity. Overall, our data confirm the involvement of BTLA in lupus pathogenesis and provide the first evidence that BTLA is a potential therapeutic target for the treatment of lupus.

immunology↗

bioRxiv2022

Epidermal maintenance of Langerhans cells relies on autophagy-regulated lipid metabolism

Macroautophagy (often-named autophagy), a catabolic process involving autophagy-related (Atg) genes, prevents accumulation of harmful cytoplasmic components and mobilizes energy reserves in long-lived and self-renewing cells. Autophagy deficiency affects antigen presentation in conventional dendritic cells (DCs) without impacting their survival. However, previous studies did not address epidermal Langerhans cells (LCs). Here, we demonstrate that deletion of either Atg5 or Atg7 in LCs leads to their gradual depletion. ATG5-deficient LCs showed metabolic dysregulation and accumulated neutral lipids. Despite increased mitochondrial respiratory capacity, they were unable to process lipids, eventually leading them to ferroptosis. Finally, metabolically impaired LCs upregulated proinflammatory transcripts and showed decreased expression of neuronal interaction receptors. Altogether, autophagy represents a critical regulator of lipid storage and metabolism in LCs, allowing their maintenance in the epidermis.

immunology↗