RT Journal Article
T1 The role of IgE in Crohn's disease by impairing the capacity of plasmacytoid dendritic cells to generate FOXP3+ Tregs
A1 De la Rocha-Muñoz, Andrés
A1 Benito Villalvilla, Cristina
A1 Olivares, David
A1 Sirvent Bernal, Sofía
A1 García-Brenes, Miguel Ángel
A1 Angelina Querencias, Alba
A1 Martín De La Cruz, Leticia
A1 Cuesta, Javier
A1 Tassinari, Paolo
A1 Jaumont, Xavier
A1 Taxonera, Carlos
A1 Palomares Gracia, Óscar
AB Background: A causal relationship between Crohn's disease (CD) and asthma is reported, but the underlying mechanisms are not fully understood. We sought to investigate the role of IgE and IgE-mediated pathways in the pathophysiology of CD.Methods: 20 CD patients, 10 allergic patients without inflammatory bowel disease, and 10 healthy donors (HD) were included in the study. Total serum IgE was quantified by ELISA. Circulating IgE+ and FcεRIα+ immune cells, as well as specific CD4+ T cell populations, were determined by flow cytometry. Gene set enrichment signatures from available single-cell (sc)RNAseq datasets of the intestine from CD patients were analyzed. Purified plasmacytoid dendritic cells (pDCs) from CD patients were cocultured with naïve CD4+ T cells to assess Tregs generation.Results: CD patients, similar to allergic non-CD patients, displayed significantly higher numbers of circulating IgE+ or FcεRIα+ immune cells than HD. The percentage of blood IgE+ or FcεRIα+ pDCs was significantly higher in CD than HD and similar to allergic non-CD patients. CD patients showed significantly higher numbers of effector memory CD4+ T cells and lower numbers of FOXP3+ Tregs than HD. scRNAseq data from CD patients confirmed that Tregs imbalance and overactivation of IgE-mediated pathways take place also in gut tissues of children and adults, suggesting IgE could interfere in the pDC-Tregs axis. In vitro functional experiments demonstrated that IgE-crosslinking on pDCs from CD patients impairs Treg generation, which was restored by the anti-IgE mAb omalizumab.Conclusions: IgE might play an unprecedented role in CD by impairing the capacity of pDCs to generate Tregs, which could represent a novel mechanism contributing to CD to be exploited for alternative therapeutic interventions.
PB Wiley
YR 2025
FD 2025-02-04
LK https://hdl.handle.net/20.500.14352/120388
UL https://hdl.handle.net/20.500.14352/120388
LA eng
NO de la Rocha-Muñoz, A., Benito-Villalvilla, C., Olivares, D., Sirvent, S., García-Brenes, M. A., Angelina, A., Martín-Cruz, L., Cuesta, J., Tassinari, P., Jaumont, X., Taxonera, C., & Palomares, O. (2025). The Role of IgE in Crohn's Disease by Impairing the Capacity of Plasmacytoid Dendritic Cells to Generate FOXP3+ Tregs. Allergy, 10.1111/all.16517.
NO Ministerio de Ciencia e Innovación
NO Comunidad de Madrid
DS Docta Complutense
RD 18 dic 2025