RT Journal Article
T1 Wnt5a Skews Dendritic Cell Differentiation to an Unconventional Phenotype with Tolerogenic Features
A1 Valencia Mahón, Jaris
A1 Hernández López, Carmen
A1 Martínez, Victor G.
A1 Hidalgo, Laura
A1 Zapata González, Agustín Gregorio
A1 Vicente López, María Ángeles
A1 Varas Fajardo, Alberto
A1 Sacedón Ayuso, Rosa
AB Dendritic cells (DCs) are critical regulators of immune responses that integrate signals from the innate and adaptive immune system and orchestrate T cell responses toward either immunity or tolerance. Growing evidence points to the Wnt signaling pathway as a pivotal piece in the immune balance and focuses on DCs as a direct target for their immunoregulatory role. Our results show that the increase in Wnt5a signaling during the differentiation of human DCs from monocytes alters their phenotype and compromises their subsequent capacity to mature in response to TLR-dependent stimuli. These Wnt5a-DCs produce scant amounts of IL-12p70 and TNF-a but increased levels of IL-10. Consequently, these Wnt5a-DCs have a reduced capacity to induce Th1 responses that promote IL-10 secretion by CD4 T cells. Changes in the transcriptional profile of Wnt5a-DCs correlate with their unconventional phenotype caused presumably by increased IL-6/IL-10 signaling during the process of DC differentiation. The effect of Wnt5a is not a consequence of b-catenin accumulation but is dependent on noncanonical Ca2+/calmodulin-dependent protein kinase II/NF-kB signaling. Our results therefore suggest that under high levels of Wnt5a, typical of the inflammatory state and sepsis, monocytes could differentiate into unconventional DCs with tolerogenic features.
PB Oxford University Press
SN 0022-1767
YR 2011
FD 2011-10-15
LK https://hdl.handle.net/20.500.14352/119147
UL https://hdl.handle.net/20.500.14352/119147
LA eng
NO Valencia J, Hernández-López C, Martínez VG, Hidalgo L, Zapata AG, Vicente Á, Varas A, Sacedón R. Wnt5a skews dendritic cell differentiation to an unconventional phenotype with tolerogenic features. J Immunol. 2011 Oct 15;187(8):4129-39. doi: 10.4049/jimmunol.1101243. Epub 2011 Sep 14. PMID: 21918189. Copy
NO Ministerio de Ciencia e Innovación
NO Instituto de Salud Carlos III
NO Universidad Complutense de Madrid
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 7 jun 2025