Abstract
The canonical Wnt signaling pathway is a master cell regulator involved in CD8+ T cell proliferation and differentiation. In human CD8+ T cells, this pathway induces differentiation into memory cells or a "stem cell memory like" population, which is preferentially present in cord blood. To better understand the role of canonical Wnt signals in neonatal or adult blood, we compared the proteins associated with β-catenin, in nonstimulated and Wnt3a-stimulated human neonatal and adult naive CD8+ T cells. Differentially recruited proteins established different complexes in adult and neonatal cells. In the former, β-catenin-associated proteins were linked to cell signaling and immunological functions, whereas those of neonates were linked to proliferation and metabolism. Wnt3a stimulation led to the recruitment and overexpression of Wnt11 in adult cells and Wnt5a in neonatal cells, suggesting a differential connexion with planar polarity and Wnt/Ca2+ noncanonical pathways, respectively. The chromatin immunoprecipitation polymerase chain reaction β-catenin was recruited to a higher level on the promoters of cell renewal genes in neonatal cells and of differentiation genes in those of adults. We found a preferential association of β-catenin with CBP in neonatal cells and with p300 in the adult samples, which could be involved in a higher self-renewal capacity of the neonatal cells and memory commitment in those of adults. Altogether, our results show that different proteins associated with β-catenin during Wnt3a activation mediate a differential response of neonatal and adult human CD8+ T cells.
Highlights
Human neonates are highly susceptible to infections by intracellular pathogens, which are a major cause of infant morbidity and mortality (World Health Organization, 2017)
We described that neonatal CD8+ T cells have a distinct transcriptomic and epigenetic programming, characterized by an inflammatory innate response, a high homeostatic proliferation rate and low signalling and cytotoxic functions (Galindo-Albarran et al, 2016)
Among the transcription factors that we found enriched in the neonatal cells were Tcf4 and Lef1, which are the responsive factors of the Wnt-signalling pathway
Summary
Human neonates are highly susceptible to infections by intracellular pathogens, which are a major cause of infant morbidity and mortality (World Health Organization, 2017). The function of neonatal T cells is considered to be immature, skewed and tolerant. Neonatal cells are capable of adult-level T-cell responses, indicating their high activation threshold (Adkins et al, 2004). The Wnt signalling pathways are master regulators of development and multiple biological functions, including antagonic roles in undifferentiated cell-renewal and differentiation (Teo and Kahn, 2010). There are 19 mammalian Wnt proteins that can be recognized by 10 frizzled (Fzd) receptors and different co-receptors, the combination of which determine the. Fo signalling pathway and outcome of the cell. The canonical pathway can be activated by
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
