A B cell-dependent pathway drives chronic lung allograft rejection after ischemia-reperfusion injury in mice
| Autor: | David M. Hwang, Betty Joe, Andrzej Chruscinski, Tatsuaki Watanabe, M. Horie, Z. Guan, Ke Fan Bei, Mingyao Liu, K. Boonstra, Tereza Martinu, Shaf Keshavjee, Stephen C. Juvet |
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| Rok vydání: | 2019 |
| Předmět: |
Graft Rejection
Male Isograft T cell Ischemia Mice Fibrosis Immunology and Allergy Medicine Animals Pharmacology (medical) B cell Autoantibodies Transplantation B-Lymphocytes Lung business.industry Graft Survival medicine.disease Allografts Disease Models Animal Lymphatic system medicine.anatomical_structure Reperfusion Injury Chronic Disease Cancer research business Reperfusion injury Lung Transplantation |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant SurgeonsREFERENCES. 19(12) |
| ISSN: | 1600-6143 |
| Popis: | Chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplant (LT). Ischemia-reperfusion injury (IRI) promotes chronic rejection (CR) and CLAD, but the underlying mechanisms are not well understood. To examine mechanisms linking IRI to CR, a mouse orthotopic LT model using a minor alloantigen strain mismatch (C57BL/10 [B10, H-2b ] → C57BL/6 [B6, H-2b ]) and isograft controls (B6→B6) was used with antecedent minimal or prolonged graft storage. The latter resulted in IRI with subsequent airway and parenchymal fibrosis in prolonged storage allografts but not isografts. This pattern of CR after IRI was associated with the formation of B cell-rich tertiary lymphoid organs within the grafts and circulating autoantibodies. These processes were attenuated by B cell depletion, despite preservation of allograft T cell content. Our observations suggest that IRI may promote B cell recruitment that drives CR after LT. These observations have implications for the mechanisms leading to CLAD after LT. |
| Databáze: | OpenAIRE |
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