Importance of EMT Factor ZEB1 in cDC1 "MutuDC Line" Mediated Induction of Th1 Immune Response.

Détails

Ressource 1Télécharger: fimmu-09-02604.pdf (5875.51 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_72C00C1A0AE9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Importance of EMT Factor ZEB1 in cDC1 "MutuDC Line" Mediated Induction of Th1 Immune Response.
Périodique
Frontiers in immunology
Auteur(s)
Smita S., Ahad A., Ghosh A., Biswas V.K., Koga M.M., Gupta B., Acha-Orbea H., Raghav S.K.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
9
Pages
2604
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
The role of Epithelial to Mesenchymal Transition (EMT) factor Zeb1 is well defined in metastasis and cancer progression but it's importance in dendritic cells (DCs) is unexplored until now. For the first time we report here that Zeb1 controls immunogenic responses of CD8α <sup>+</sup> conventional Type-I (cDC1) DCs. We found that ZEB1 expression increases significantly after TLR9 stimulation and its depletion impairs activation, co-stimulation and secretion of important cytokines like IL-6, IL-10 and IL-12 in cDC1 MutuDC line. We further confirmed our findings in primary cDC1 DCs derived from bone marrow. Co-culture of these Zeb1 knock down (KD) DCs with OT-II CD4 <sup>+</sup> T helper cells skewed their differentiation toward Th2 subtype. Moreover, adoptive transfer of activated Zeb1 KD DCs cleared intestinal worms in helminth infected mice by increasing Th2 responses <i>in vivo</i> . Integrative genomic analysis showed Zeb1 as an activator of immune response genes in cDC1 MutuDCs as compared to other pathway genes. In addition, differentially regulated genes in Zeb1 KD RNA-seq showed significant enrichment of Th2 activation pathways supporting our <i>in vitro</i> findings. Mechanistically, we showed that decreased IL-12 secreted by Zeb1 KD DCs is the plausible mechanism for increased Th2 differentiation. Collectively our data demonstrate that Zeb1 could be targeted in DCs to modulate T-cell mediated adaptive immune responses.
Mots-clé
ZEB1, cDC1 dendritic cells, integrative genomics, Th2 response, ChIP-seq, RNA-seq, helminth infection, immune modulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/11/2018 11:56
Dernière modification de la notice
20/08/2019 15:30
Données d'usage