TY - JOUR
T1 - Scrib and Dlg1 polarity proteins regulate Ag presentation in human dendritic cells
AU - Barreda, Dante
AU - Ramón-Luing, Lucero A.
AU - Duran-Luis, Olivia
AU - Bobadilla, Karen
AU - Chacón-Salinas, Rommel
AU - Santos-Mendoza, Teresa
N1 - Publisher Copyright:
©2020 Society for Leukocyte Biology
PY - 2020/9/1
Y1 - 2020/9/1
N2 - We recently reported, for the first time, the expression and regulation of the PDZ polarity proteins Scrib and Dlg1 in human APCs, and also described the viral targeting of these proteins by NS1 of influenza A virus in human dendritic cells (DCs). Scrib plays an important role in reactive oxygen species (ROS) production in Mϕs and uropod formation and migration in T cells, while Dlg1 is important for T cell downstream activation after Ag recognition. Nevertheless, the functions of these proteins in human DCs remain unknown. Here, we knocked-down the expression of both Scrib and Dlg1 in human DCs and then evaluated the expression of co-stimulatory molecules and cytokine production during maturation. We demonstrated that Scrib is necessary for adequate CD86 expression, while Dlg1 is important for CD83 up-regulation and IL-6 production upon maturation, suggesting that Scrib and Dlg1 participate in separate pathways in DCs. Additionally, both proteins are required for adequate IL-12 production after maturation. Furthermore, we showed that the inefficient maturation of DCs induced by Scrib or Dlg1 depletion leads to impaired T cell activation. Our results revealed the previously unknown contribution of Scrib and Dlg1 in human DCs pivotal functions, which may be able to impact innate and adaptive immune response.
AB - We recently reported, for the first time, the expression and regulation of the PDZ polarity proteins Scrib and Dlg1 in human APCs, and also described the viral targeting of these proteins by NS1 of influenza A virus in human dendritic cells (DCs). Scrib plays an important role in reactive oxygen species (ROS) production in Mϕs and uropod formation and migration in T cells, while Dlg1 is important for T cell downstream activation after Ag recognition. Nevertheless, the functions of these proteins in human DCs remain unknown. Here, we knocked-down the expression of both Scrib and Dlg1 in human DCs and then evaluated the expression of co-stimulatory molecules and cytokine production during maturation. We demonstrated that Scrib is necessary for adequate CD86 expression, while Dlg1 is important for CD83 up-regulation and IL-6 production upon maturation, suggesting that Scrib and Dlg1 participate in separate pathways in DCs. Additionally, both proteins are required for adequate IL-12 production after maturation. Furthermore, we showed that the inefficient maturation of DCs induced by Scrib or Dlg1 depletion leads to impaired T cell activation. Our results revealed the previously unknown contribution of Scrib and Dlg1 in human DCs pivotal functions, which may be able to impact innate and adaptive immune response.
KW - Ag presentation
KW - Dlg1
KW - PDZ polarity proteins
KW - Scrib
KW - dendritic cells
UR - http://www.scopus.com/inward/record.url?scp=85083458665&partnerID=8YFLogxK
U2 - 10.1002/JLB.4MA0320-544RR
DO - 10.1002/JLB.4MA0320-544RR
M3 - Artículo
C2 - 32293058
AN - SCOPUS:85083458665
SN - 0741-5400
VL - 108
SP - 883
EP - 893
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -