IL-17A mediates early post-transplant lesions after heterotopic trachea allotransplantation in Mice
| Autor: | Myriam Remmelink, Yoichiro Iwakura, Philippe Lemaitre, Alain Le Moine, Michel Goldman, Louis-Marie Charbonnier, B. Vokaer, Marc Estenne, Oberdan Leo |
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| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Graft Rejection Pathology medicine.medical_specialty Transplantation Heterotopic medicine.medical_treatment T cell lcsh:Medicine Primary Graft Dysfunction Bronchiolitis obliterans CD4-Positive T-Lymphocytes -- immunology -- metabolism Biology Mice Interleukin-17 -- deficiency -- genetics -- metabolism medicine Lung transplantation Animals Transplantation Homologous Trachea -- metabolism -- pathology -- transplantation lcsh:Science Reperfusion Injury -- complications Mice Knockout Multidisciplinary Receptors Antigen T-Cell gamma-delta -- metabolism lcsh:R Interleukin-17 Receptors Antigen T-Cell gamma-delta Sciences bio-médicales et agricoles Lung Transplantation -- adverse effects medicine.disease Graft Rejection -- immunology -- metabolism -- pathology Transplant rejection Transplantation Trachea medicine.anatomical_structure Reperfusion Injury Immunology lcsh:Q Stem cell Allotransplantation Lung Transplantation Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 7, p e70236 (2013) PloS one, 8 (7 |
| ISSN: | 1932-6203 |
| Popis: | Primary graft dysfunction (PGD) and bronchiolitis obliterans (BO) are the leading causes of morbidity and mortality after lung transplantation. Reports from clinical and rodent models suggest the implication of IL-17A in either PGD or BO. We took advantage of the heterotopic trachea transplantation model in mice to study the direct role of IL-17A in post-transplant airway lesions. Across full MHC barrier, early lesions were controlled in IL-17A(-/-) or anti-IL17 treated recipients. In contrast, IL-17A deficiency did not prevent subsequent obliterative airway disease (OAD). Interestingly, this early protection occurred also in syngeneic grafts and was accompanied by a decrease in cellular stress, as attested by lower HSP70 mRNA levels, suggesting the involvement of IL-17A in ischemia-reperfusion injury (IRI). Furthermore, persistence of multipotent CK14(+) epithelial stem cells underlined allograft protection afforded by IL-17A deficiency or neutralisation. Recipient-derived γδ(+) and CD4(+) T cells were the major source of IL-17A. However, lesions still occurred in the absence of each subset, suggesting a high redundancy between the innate and adaptive IL-17A producing cells. Notably, a double depletion significantly diminished lesions. In conclusion, this work implicated IL-17A as mediator of early post-transplant airway lesions and could be considered as a potential therapeutic target in clinical transplantation. Journal Article Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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