Biology subjects

Daamen, A.

Publications and source records attributed to Daamen, A..

3 recordsLinked to original sources

bioRxiv2026

Comprehensive Transcriptomic Analysis of Atopic Dermatitis Patients Documents the Spectrum of Molecular Abnormalities and the Response to Treatment

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and barrier dysfunction. To define the molecular architecture of AD in greater detail, we integrated lesional (LES) and non-lesional (NLS) transcriptomic data from multiple datasets using gene expression data from normal skin and psoriasis (PSO) and nummular eczema (NME) cohorts as reference. Gene set variation analysis revealed that adult AD exhibits broad immune activation and consistent barrier impairment in both LES and NLS skin, whereas pediatric AD is dominated by IL-1-driven inflammation with minimal barrier alteration. Comparative analyses showed stronger Th2 and myeloid activity in AD, metabolic enrichment in PSO, and complement and NK cell activation in NME. Longitudinal profiling identified temporal variation in Th1, Th2 and IFN pathways in AD skin. An eczema immune and cellular score, ECZECIS, was developed to quantify transcriptomic abnormalities and correlated with clinical improvement following dupilumab therapy. Among all treatments analyzed, dupilumab produced the most extensive reduction of immune and cytokine pathway activity in skin and attenuated systemic immune activation in blood. These findings delineate distinct immune and barrier signatures across age groups and disease types and establish ECZECIS as a quantitative biomarker for monitoring molecular treatment response in AD.

bioinformatics↗

bioRxiv2024

Granulocyte colony-stimulating factor protects against arthritogenic alphavirus pathogenesis in a type I IFN-dependent manner

Arthritogenic alphaviruses cause disease characterized by fever, rash, and incapacitating joint pain. Alphavirus infection stimulates robust inflammatory responses in infected hosts, leading to the upregulation of several cytokines, including granulocyte colony-stimulating factor (G-CSF). G-CSF is secreted by endothelial cells, fibroblasts, macrophages, and monocytes and binds to colony stimulating factor 3 receptor (CSF3R, also known as G-CSFR) on the surface of myeloid cells. G-CSFR signaling initiates proliferation, differentiation, and maturation of myeloid cells, especially neutrophils. Importantly, G-CSF has been found at high levels in both the acute and chronic phases of chikungunya disease; however, the role of G-CSF in arthritogenic alphavirus disease remains unexplored. Here, we sought to test the effect of G-CSF on chikungunya virus (CHIKV) and Mayaro virus (MAYV) infection using G-CSFR-deficient mice (G-CSFR-/-). We observed sustained weight loss in G-CSFR-/- mice following viand MAYV infection compared to wild-type mice. Furthermore, G-CSFR-/- mice had a significantly higher percentage of inflammatory monocytes and reduction in neutrophils throughout infection. The difference in weight loss in G-CSFR-/- mice induced by alphavirus infection was corrected by blocking type I IFN signaling. In summary, these studies show that type I IFN signaling contributes to G-CSFR mediated control of arthritogenic alphavirus disease.

immunology↗

bioRxiv2024

Obesity-Associated Changes in Immune Cell Dynamics During Alphavirus Infection Revealed by Single Cell Transcriptomic Analysis

Obesity induces diverse changes in host immunity, resulting in worse disease outcomes following infection with various pathogens, including arthritogenic alphaviruses. However, the impact of obesity on the functional landscape of immune cells during arthritogenic alphavirus infection remains unexplored. Here, we used single-cell RNA sequencing (scRNA-seq) to dissect the blood and tissue immune responses to Mayaro virus (MAYV) infection in lean and obese mice. Footpad injection of MAYV caused significant shifts in immune cell populations and induced robust expression of interferon response and proinflammatory cytokine genes and related pathways in both blood and tissue. In MAYV-infected lean mice, analysis of the local tissue response revealed a unique macrophage subset with high expression of IFN response genes that was not found in obese mice. This was associated with less severe inflammation in lean mice. These results provide evidence for a unique macrophage population that may contribute to the superior capacity of lean mice to control arthritogenic alphavirus infection. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/617696v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@11e9cbdorg.highwire.dtl.DTLVardef@c44512org.highwire.dtl.DTLVardef@192da94org.highwire.dtl.DTLVardef@4c5ea5_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIObesity worsens disease outcomes following arthritogenic alphavirus infection. C_LIO_LIArthritogenic alphavirus infection causes significant shifts in immune cell populations in the blood and footpad. C_LIO_LIBlood monocytes from lean mice had higher expression of interferon response genes at the later stage of infection. C_LIO_LIFootpads in lean mice have an expanded population of F4/80lo macrophages with an intense interferon response gene signature before and after alphavirus infection that is not found in obese mice. C_LIO_LIMacrophages in obese mice express lower levels of interferon response genes, have a unique necroptosis signature, and higher F4/80 expression. C_LI

immunology↗