Podocalyxin Expressed in Antigen Presenting Cells Promotes Interaction With T Cells and Alters Centrosome Translocation to the Contact Site

Abstract

Podocalyxin (PODXL), a cell surface sialomucin expressed in diverse types of normal and malignant cells, mediates cellular adhesion to extracellular matrix and cell-to-cell interaction. A previous study reported the expression of PODXL protein on monocytes undergoing macrophage differentiation, yet the expression of this molecule in other antigen presenting cells (APCs) and its function in the immune system still remain undetermined. In this study, we report that PODXL is expressed in human monocyte-derived immature dendritic cells at both the mRNA and protein levels. Following dendritric cells maturation using pro-inflammatory stimuli, PODXL expression level decreased substantially. Furthermore, we found that PODXL expression is positively regulated by IL-4 through MEK/ERK and JAK3/STAT6 signaling pathways. Our results revealed a polarized distribution of PODXL during the interaction of APCs with CD4+ T cells, partially colocalizing with F-actin. Notably, PODXL overexpression in APCs promoted their interaction with CD4+ T cells and CD8+ T cells and decreased the expression of MHC-I, MHC-II, and the costimulatory molecule CD86. In addition, PODXL reduced the translocation of CD4+ T-cell centrosome toward the APC-contact site. These findings suggest a regulatory role for PODXL expressed by APCs in immune responses, thus representing a potential target for therapeutic blockade in infection and cancer.

Characterization and mechanisms of radioresistant lung squamous cell carcinoma cell lines

“…In existing research reports, among the upregulated differential genes, MBD4 is involved in the DNA repair mechanism, 35 and TIMP3 and PODXL are related to ECM and cell adhesion. 36 , 37 …”

“…We used TMT quantitative marker proteome technology to compare the LUSC radiotherapy‐resistant cell H2170DR with its parental cell H2170, and we screened out 27 differences related to biological pathways such as DNA damage repair, ECM‐receptor, cell migration, and cell adhesion genes. In existing research reports, among the upregulated differential genes, MBD4 is involved in the DNA repair mechanism, 35 and TIMP3 and PODXL are related to ECM and cell adhesion 36,37 …”

“…In existing research reports, among the upregulated differential genes, MBD4 is involved in the DNA repair mechanism, 35 and TIMP3 and PODXL are related to ECM and cell adhesion. 36,37 In summary, LUSC radiotherapy-resistant cell lines can be obtained by fractionated radiotherapy of LUSC cell lines. Using this preclinical cell model, we can further explore potential molecular markers of radioresistance in LUSC.…”