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

研究成果: Article査読

8 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3377-3389
ページ数13
ジャーナルAmerican Journal of Transplantation
19
12
DOI
出版ステータスPublished - 2019 12 1
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 移植
  • 薬理学(医学)

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