| First Author | Masli S | Year | 2006 |
| Journal | Int Immunol | Volume | 18 |
| Issue | 5 | Pages | 689-99 |
| PubMed ID | 16569680 | Mgi Jnum | J:108549 |
| Mgi Id | MGI:3624227 | Doi | 10.1093/intimm/dxl006 |
| Citation | Masli S, et al. (2006) Thrombospondin orchestrates the tolerance-promoting properties of TGF{beta}-treated antigen-presenting cells. Int Immunol 18(5):689-99 |
| abstractText | Eye-derived antigen-presenting cells (APCs) are known to contribute to the immune privilege status of the eye by inducing a form of peripheral tolerance that deviates T(h)1 type of pro-inflammatory immune responses. Similar systemic tolerance can also be induced by non-ocular APCs exposed to transforming growth factor beta (TGFbeta) in vitro. Such APCs were found to express enhanced levels of thrombospondin (TSP)-1, an extracellular matrix (ECM) protein. In this report, we analyzed the significance of TSP-1 in conferring tolerance-inducing properties on APCs. While TSP-treated APCs matched TGFbeta-treated APCs in their functional ability to induce systemic tolerance, a deficiency of TSP-1 or its receptor CD36 prevented APCs from becoming tolerogenic in response to TGFbeta. Exogenous TSP-1 restored tolerogenic ability of TGFbeta-treated TSP-1 null APCs. Both TGFbeta-treated TSP-1 null and CD36 knockout APCs failed to inhibit IL-12 secretion. Furthermore, TGFbeta-treated TSP-1 null APCs, unlike similarly treated wild-type APCs, failed to increase secretion of active TGFbeta. Similar to TGFbeta, TSP could also up-regulate expression of MIP-2, TGFbeta2 and tumor necrosis factor alpha-all of which are required for tolerance induced by TGFbeta-treated APCs. We conclude that TSP-1, an ECM protein induced by TGFbeta treatment, orchestrates the changes in APC functional programs that equip these cells to promote tolerance of the eye-derived type. |
