Biology subjects

T'Jonck, W.

Publications and source records attributed to T'Jonck, W..

3 recordsLinked to original sources

bioRxiv2026

Diverse lung challenges elicit a conserved monocyte-to-macrophage differentiation blueprint

Alveolar macrophages (AM) form a first line of defence to lung insults. These insults often lead to replacement of foetal-derived tissue-resident AMs (fAMs) by monocyte-derived AMs (mono-AMs) with different functionality, which impacts lung immunity long-term. However, whether these alterations are conserved or insult-specific is not well understood. Here, we show that respiratory syncytial virus (RSV) infection remodels the AM compartment long-term. We perform comparative analyses of fAMs and mono-AMs after RSV infection, influenza (IAV) infection and clodronate liposome administration to derive rules governing the functional and transcriptional changes in AM across insults. We identify a crucial tissue integration checkpoint of CD11b+ mono-AMs which involves acquisition of proliferative capacity and requires EGR2-mediated transcriptional rewiring. Mono-AMs elicited by RSV, influenza or clodronate liposomes have a hard-wired ontogeny-dependent stereotypical profile of transcription, metabolism and enhanced immunoreactivity despite a substantially different inflammatory environment during differentiation; accordingly, mono-AMs, whether elicited by infection or sterile depletion, protect from subsequent S. pneumoniae infection. By contrast, fAMs are more susceptible to subtle, context-dependent transcriptional alterations. Our findings highlight that long-term changes in the AM compartment show origin-dependent phenotypic divergence and that mono-AM integration follows a hard-wired trajectory fine-tuned by environmental factors.

immunology↗

bioRxiv2024

Epithelial memory after respiratory viral infection results in long-lasting enhancement of antigen presentation

BackgroundViral lower respiratory tract infections (LRTIs) can reduce severity of subsequent LRTIs but have also been linked to respiratory allergy development and exacerbation. Here, we show that viral LRTI can imprint lung epithelial cells (LECs), leading to long-term phenotypic and functional changes in their response to subsequent challenges. MethodsMice were infected via intranasal administration of respiratory syncytial virus (RSV). After 28 days, LECs were isolated using cold dispase digestion followed by magnetic-activated cell sorting. Epigenetic changes were assessed using CUT&RUN, while transcriptional changes were evaluated using NanoString and qPCR. Flow cytometry was employed to measure cell surface MHC levels, antigen uptake and processing rates, and OT-I proliferation. ResultsWe identified epigenetic and transcriptomic changes in murine LECs 28 days post respiratory syncytial virus (RSV) infection after recovery in genes associated with major histocompatibility complexes (MHC). Lasting upregulation of MHC-I and MHC-II was further increased following in vivo LPS stimulation. Importantly, MHC upregulation was associated with increased antigen uptake and processing, as well as increased antigen presentation to T cells. ConclusionsOur data suggest that LRTI can induce long-term upregulation of antigen-presentation by LECs, thus facilitating local T cell responses to microbial antigens and allergens, potentially enhancing immunity or in susceptible hosts respiratory allergy.

immunology↗

bioRxiv2021

The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair

Alveolar macrophages are the most abundant macrophages in the healthy lung where they play key roles in homeostasis and immune surveillance against air-borne pathogens. Tissue-specific differentiation and survival of alveolar macrophages relies on niche-derived factors, such as colony stimulating factor 2 (CSF-2) and transforming growth factor beta (TGF-{beta}). However, the nature of the downstream molecular pathways that regulate the identity and function of alveolar macrophages and their response to injury remains poorly understood. Here, we identify that the transcriptional factor EGR2 is an evolutionarily conserved feature of lung alveolar macrophages and show that cell-intrinsic EGR2 is indispensable for the tissue-specific identity of alveolar macrophages. Mechanistically, we show that EGR2 is driven by TGF-{beta} and CSF-2 in a PPAR-{gamma}-dependent manner to control alveolar macrophage differentiation. Functionally, EGR2 was dispensable for lipid handling, but crucial for the effective elimination of the respiratory pathogen Streptococcus pneumoniae. Finally, we show that EGR2 is required for repopulation of the alveolar niche following sterile, bleomycin-induced lung injury and demonstrate that EGR2-dependent, monocyte-derived alveolar macrophages are vital for effective tissue repair following injury. Collectively, we demonstrate that EGR2 is an indispensable component of the transcriptional network controlling the identity and function of alveolar macrophages in health and disease. One Sentence SummaryEGR2 controls alveolar macrophage function in health and disease

immunology↗