Role of syndecan-1 in the interaction between dendritic cells and T cells

• Published in: PloS one 2020-07, Vol.15 (7), p.e0230835-e0230835
• Main Authors: Kouwenberg, M, Rops, A, Bakker-van Bebber, M, Diepeveen, L, Götte, M, Hilbrands, L, van der Vlag, J
• Format: Article
• Language: English
• Subjects: Apoptosis; Biology and Life Sciences; Bone marrow; Bone marrow transplantation; Cell activation; Cell growth; Cell proliferation; Cell surface; Cell survival; Chemokines; Concanavalin A; Cytokines; Dendritic cells; Flow cytometry; Heart transplantation; Heparan sulfate; Immunology; Immunomodulation; Inflammation; Interleukin 17; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medicine and Health Sciences; Mixed leukocyte reaction; Motility; Nephrology; Neutrophils; Pathogens; Phenotypes; Proteoglycans; Research and Analysis Methods; Sepsis; Stimulation; Sulfates; Survival; Syndecan; Transplants & implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0230835

Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that can bind cytokines and chemokines via its heparan sulfate side chains, and has immunomodulatory properties in experimental models. Sdc-1 expression has been reported on dendritic cells (DC) and T cells. The potential role of Sdc-1 in DC—T cell interaction has not been investigated yet. We postulate that Sdc-1 is involved in DC–T cell interaction and may influence graft survival in an allogeneic transplant model. Sdc-1 expression on bone marrow-derived DC and T cells was analyzed by flow cytometry. Unstimulated and LPS stimulated Sdc-1 deficient DC were evaluated in vitro for phenotype and stimulatory capacity in mixed lymphocyte reaction. Sdc-1 deficient T cells were evaluated for proliferative capacity and differentiation in a mixed lymphocyte reaction and a proliferation assay. Allograft survival was evaluated in a fully MHC mismatched heterotopic heart transplant model, with either Sdc-1 deficient donors or recipients. Sdc-1 was expressed on the cell surface of unstimulated and LPS matured DC. Sdc-1 deficiency had no effect on expression of co-stimulatory molecules, cytokine production or T cell stimulatory capacity as compared to WT DC. Sdc-1 expression was not detectable on WT T cells, although intracellular Sdc-1 expression could be demonstrated after ConA activation. Sdc-1 deficient T cells showed reduced proliferation upon DC or ConA stimulation and reduced IL-17 production upon ConA stimulation, compared to WT T cells. Sdc-1 deficiency of either allograft or recipient did not prolong allograft survival. In conclusion, Sdc-1 is expressed on the cell surface of DC, where its absence does not affect DC phenotype or T cell stimulatory capacity. Sdc-1 is intracellularly expressed in ConA activated T cells. Sdc-1 deficiency in T cells results in a reduced proliferative response in vitro, as induced by DC and ConA. Sdc-1 deficiency in donor or recipient does not affect allograft survival.