Biology subjects

Bouteau, A.

Publications and source records attributed to Bouteau, A..

6 recordsLinked to original sources

bioRxiv2025

Langerhans Cells Drive Tfh and B Cell Responses Independent of Canonical Cytokine Signals

Dendritic cells (DCs) are key regulators of adaptive immunity, guiding T helper (Th) cell differentiation through antigen presentation, co-stimulation, and cytokine production. However, in steady-state conditions, certain DC subsets, such as Langerhans cells (LCs), induce T follicular helper (Tfh) cells and B cell responses without inflammatory stimuli. Using multiple mouse models and in vitro systems, we investigated the mechanisms underlying steady-state LC-induced adaptive immune responses. We found that LCs drive germinal center Tfh and B cell differentiation and antibody production independently of interleukin-6 (IL-6), type-I interferons, and ICOS ligand (ICOS-L) signaling, which are critical in inflammatory settings. Instead, these responses relied on CD80/CD86-mediated co-stimulation. Our findings challenge the conventional three-signal paradigm by demonstrating that cytokine signaling is dispensable for LC-mediated Tfh and B cell responses in steady-state. These insights provide a framework for understanding homeostatic immunity and the immune systems role in maintaining tolerance or developing autoimmunity under non-inflammatory conditions. SUMMARY STATEMENTLangerhans cells (LCs) drive germinal center Tfh and B cell responses in steady-state conditions independently of IL-6, type-I interferons, and ICOS ligand, challenging the established cytokine-centric model of T cell differentiation.

immunology↗

bioRxiv2023

Dendritic Cells Overcome Cre/Lox Induced Gene Deficiency by Siphoning Material From Neighboring Cells Using Intracellular Monitoring - a Novel Mechanism of Antigen Acquisition

Macrophages and dendritic cells (DCs) in peripheral tissue interact closely with their local microenvironment by scavenging protein and nucleic acids released by neighboring cells. Material transfer between cell types is necessary for pathogen detection and antigen presentation, but thought to be relatively limited in scale. Recent reports, however, demonstrate that the quantity of transferred material can be quite large when DCs are in direct contact with live cells. This observation may be problematic for conditional gene deletion models that assume gene products will remain in the cell they are produced in. Here, we investigate whether conditional gene deletions induced by the widely used Cre/Lox system can be overcome at the protein level in DCs. Of concern, using the human Langerin Cre mouse model, we find that epidermal Langerhans cells and CD11b+CD103+ mesenteric DCs can overcome gene deletion if the deleted gene is expressed by neighboring cells. Surprisingly, we also find that the mechanism of material transfer does not resemble known mechanisms of antigen uptake, is dependent on extra- and intracellular calcium, PI3K, and scavenger receptors, and mediates a majority of material transfer to DCs. We term this novel process intracellular monitoring, and find that it is specific to DCs, but occurs in all murine DC subsets tested, as well as in human DCs. Transferred material is successfully presented and cross presented on MHC-II and MHC-I, and occurs between allogeneic donor and acceptors cells--implicating this widespread and unique process in immunosurveillance and organ transplantation. ONE SENTENCE SUMMARYDendritic cells maintain RNA and protein levels for conditionally deleted genes by siphoning material from neighboring cells using a novel mechanism.

immunology↗

bioRxiv2021

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses

Nucleoside modified mRNA combined with Acuitas Therapeutics lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper cells (Tfh) and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, the still high antibody titers were sufficient to confer protection towards lethal viral challenges. We further found that IL-6, but not neutrophils, was required to generate Tfh cells and antibody responses. In summary, here we bring evidence that the mRNA-LNP platform can support protective adaptive immune responses in the absence of specific DC subsets through an IL-6 dependent and neutrophil independent mechanism.

immunology↗

bioRxiv2021

The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against coronavirus disease in 2019 (COVID-19). Clinical trials and ongoing vaccinations present with very high protection levels and varying degrees of side effects. However, the nature of the reported side effects remains poorly defined. Here we present evidence that LNPs used in many preclinical studies are highly inflammatory in mice. Intradermal injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate. In summary, here we show that the LNPs used for many preclinical studies are highly inflammatory. Thus, their potent adjuvant activity and reported superiority comparing to other adjuvants in supporting the induction of adaptive immune responses likely stem from their inflammatory nature. Furthermore, the preclinical LNPs are similar to the ones used for human vaccines, which could also explain the observed side effects in humans using this platform.

immunology↗

bioRxiv2019

Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the niche cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells (LCs) led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken in consideration at data interpretation.

immunology↗

bioRxiv2019

Immune cell-specific Cre reporter mouse labels a subset of CNS neurons

HuLangerin-Cre-YFPf/f mice were generated to specifically mark a subset of antigen presenting immune cells, called Langerhans cells (LCs). During histological characterization of these mice, we found that, in addition to LCs an uncharacterized cell population in the central nervous system (CNS) also expressed YFP. In this study, we found that the CNS YFP+ cells were negative for microglia and astrocyte markers, but they expressed mature neuronal marker NeuN and showed neuronal localization/morphology. Thus, these mice might be used to study the ontogeny, migration and the role of a subset of CNS neurons.

neuroscience↗