A B cell–dependent pathway drives chronic lung allograft rejection after ischemia–reperfusion injury in mice

Tatsuaki Watanabe, Tereza Martinu, Andrzej Chruscinski, Kristen Boonstra, Betty Joe, Miho Horie, Zehong Guan, Ke Fan Bei, David M. Hwang, Mingyao Liu, Shaf Keshavjee, Stephen C. Juvet

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3377-3389
Number of pages13
JournalAmerican Journal of Transplantation
Volume19
Issue number12
DOIs
Publication statusPublished - 2019 Dec 1
Externally publishedYes

Keywords

  • B cell biology
  • animal models: murine
  • basic (laboratory) research/science
  • bronchiolitis obliterans (BOS)
  • immunobiology
  • immunosuppression/immune modulation
  • innate immunity
  • lung (allograft) function/dysfunction
  • lung transplantation/pulmonology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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