| First Author | Wang F | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 7 | Pages | 844-50 |
| PubMed ID | 27213689 | Mgi Jnum | J:259591 |
| Mgi Id | MGI:6141927 | Doi | 10.1038/ni.3462 |
| Citation | Wang F, et al. (2016) Inhibition of T cell receptor signaling by cholesterol sulfate, a naturally occurring derivative of membrane cholesterol. Nat Immunol 17(7):844-50 |
| abstractText | Most adaptive immune responses require the activation of specific T cells through the T cell antigen receptor (TCR)-CD3 complex. Here we show that cholesterol sulfate (CS), a naturally occurring analog of cholesterol, inhibits CD3 ITAM phosphorylation, a crucial first step in T cell activation. In biochemical studies, CS disrupted TCR multimers, apparently by displacing cholesterol, which is known to bind TCRbeta. Moreover, CS-deficient mice showed heightened sensitivity to a self-antigen, whereas increasing CS content by intrathymic injection inhibited thymic selection, indicating that this molecule is an intrinsic regulator of thymocyte development. These results reveal a regulatory role for CS in TCR signaling and thymic selection, highlighting the importance of the membrane microenvironment in modulating cell surface receptor activation. |
