Biology subjects

Leyva-Castillo, J. M.

Publications and source records attributed to Leyva-Castillo, J. M..

3 recordsLinked to original sources

bioRxiv2024

IL-4 receptor alpha blockade in mice reduces skin inflammation, systemic response and the atopic march.

Atopic dermatitis (AD) commonly precedes food allergy and asthma in the atopic march. Epicutaneous (EC) sensitization in mice with ovalbumin (OVA) results in allergic skin inflammation that mimics AD and promotes food anaphylaxis or asthma following a gastric or intranasal challenge with OVA, respectively. Using our mouse model of EC sensitization with OVA we evaluate whether anti-IL-4R blocking antibody improve allergic skin inflammation and impact the atopic march. IL-4R blockade at the end of EC sensitization decreased allergic skin inflammation in OVA-sensitized mice, evidenced by significantly decreased eosinophil infiltration, decrease production of IL-4, IL-13 by OVA- restimulated splenocytes and reduced serum levels OVA-specific IgE. However, late IL- 4R blockade did not affect food anaphylaxis or airway inflammation in EC sensitized mice following an oral or intranasal challenge with OVA. IL-4R blockade at the beginning of EC sensitization not only impact allergic skin inflammation and systemic response to the antigen, but also decreased food anaphylaxis or airway inflammation following OVA challenge. These results suggest that the blockade of sensitization through the skin by IL-4R blockade could impact the atopic march.

immunology↗

bioRxiv2024

Ixodes ricinus bites promote allergic skin inflammation and intestinal tuft and mast cell expansion in mice.

BackgroundTick bites often promote local allergic reactions in the skin and predispose to red meat allergy. The mechanisms involved in these processes are not fully understood. Here we investigated the local changes to the skin and intestine induced by tick bites. MethodsC3H/HEN or Balb/c mice were subjected to either tick bites by Ixodes ricinus (I. ricinus) or mechanical skin injury. Skin or intestine was analyzed a different time point by transcriptomic and histological techniques. ResultsOur results indicate that I. ricinus bites promote epidermal hyperplasia, spongiosis and an accumulation of eosinophils and mast cells in the bitten skin. In addition, I. ricinus bites promote the expression of genes and activate pathways also induced by mechanical skin injury elicited by tape stripping. Remarkably, similar to tape stripping, I. ricinus bites promote an increase in total serum IgE, and intestinal tuft cell and mast cell expansion. ConclusionI. ricinus bites in mice promote cutaneous inflammation that resembles allergic skin inflammation, as well as intestinal changes that could play a role in the predisposition to red meat allergy.

immunology↗

bioRxiv2023

Multi-modal skin atlas associates a multicellular immune-stromal community with altered cornification and T cell expansion in atopic dermatitis

In healthy skin, a cutaneous immune system maintains the balance between tolerance towards innocuous environmental antigens and immune responses against pathological agents. In atopic dermatitis (AD), barrier and immune dysfunction result in chronic tissue inflammation. Our understanding of the skin tissue ecosystem in AD remains incomplete with regard to the hallmarks of pathological barrier formation, and cellular state and clonal composition of disease-promoting cells. Here, we generated a multi-modal cell census of 310,691 cells spanning 86 cell subsets from whole skin tissue of 19 adult individuals, including non-lesional and lesional skin from 11 AD patients, and integrated it with 396,321 cells from four studies into a comprehensive human skin cell atlas in health and disease. Reconstruction of human keratinocyte differentiation from basal to cornified layers revealed a disrupted cornification trajectory in AD. This disrupted epithelial differentiation was associated with signals from a unique immune and stromal multicellular community comprised of MMP12+ dendritic cells (DCs), mature migratory DCs, cycling ILCs, NK cells, inflammatory CCL19+ IL4I1+ fibroblasts, and clonally expanded IL13+IL22+IL26+ T cells with overlapping type 2 and type 17 characteristics. Cell subsets within this immune and stromal multicellular community were connected by multiple inter-cellular positive feedback loops predicted to impact community assembly and maintenance. AD GWAS gene expression was enriched both in disrupted cornified keratinocytes and in cell subsets from the lesional immune and stromal multicellular community including IL13+IL22+IL26+ T cells and ILCs, suggesting that epithelial or immune dysfunction in the context of the observed cellular communication network can initiate and then converge towards AD. Our work highlights specific, disease-associated cell subsets and interactions as potential targets in progression and resolution of chronic inflammation.

molecular biology↗