| First Author | Keane MP | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 1 | Pages | 511-9 |
| PubMed ID | 17182591 | Mgi Jnum | J:141922 |
| Mgi Id | MGI:3820028 | Doi | 10.4049/jimmunol.178.1.511 |
| Citation | Keane MP, et al. (2007) IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans syndrome. J Immunol 178(1):511-9 |
| abstractText | Acute allograft rejection is considered to be a predominately type 1 immune mediated response to the donor alloantigen. However, the type 2 immune mediated response has been implicated in multiple fibroproliferative diseases. Based on the fibro-obliterative lesion found during bronchiolitis obliterans syndrome (BOS), we hypothesized that the type 2 immune mediated response is involved in chronic lung allograft rejection. Specifically, whereas acute rejection is, in part, a type 1 immune response, chronic rejection is, in part, a type 2 immune response. We found the type 2 cytokine, IL-13, to be elevated and biologically active in human bronchoalveolar lavage fluid during BOS. Translational studies using a murine model of BOS demonstrated increased expression of IL-13 and its receptors that paralleled fibro-obliteration. In addition, in vivo neutralization of IL-13 reduced airway allograft matrix deposition and murine BOS, by a mechanism that was independent of IL-4. Furthermore, using IL-13Ralpha2(-/-) mice, we found increased fibro-obliteration. Moreover, anti-IL-13 therapy in combination with cyclosporin A had profound effects on reducing murine BOS. This supports the notion that IL-13 biological axis plays an important role during the pathogenesis of BOS independent of the IL-4 biological axis. |
