| First Author | Chung JS | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 6 | Pages | 1794-9 |
| PubMed ID | 21469128 | Mgi Jnum | J:176484 |
| Mgi Id | MGI:5291901 | Doi | 10.1002/eji.201041233 |
| Citation | Chung JS, et al. (2011) Inhibition of T-cell activation by syndecan-4 is mediated by CD148 through protein tyrosine phosphatase activity. Eur J Immunol 41(6):1794-9 |
| abstractText | Most coinhibitory receptors regulate T-cell responses through an ITIM that recruits protein tyrosine phosphatases (PTPs) to mediate inhibitory function. Because syndecan-4 (SD-4), the coinhibitor for DC-associated heparan sulfate proteoglycan integrin ligand (DC-HIL), lacks such an ITIM, we posited that SD-4 links with a PTP in an ITIM-independent manner. We show that SD-4 associates constitutively with the intracellular protein syntenin but not with the receptor-like PTP CD148 on human CD4(+) T cells. Binding to DC-HIL allowed SD-4 to assemble with CD148 through the help of syntenin as a bridge, and this process upregulated the PTP activity of CD148, which is required for SD-4 to mediate DC-HIL's inhibitory function. Using a mouse model, we found SD-4 to be located away from the immunological synapse formed between T cells and APCs during activation of T cells. These findings indicate that SD-4 is unique among known T-cell coinhibitors, in employing CD148 to inhibit T-cell activation at a site distal from the synapse. |
