An obligatory role for club cells in preventing obliterative bronchiolitis in lung transplants.
An obligatory role for club cells in preventing obliterative bronchiolitis in lung transplants.
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俱乐部细胞在预防肺移植中闭塞性细支气管炎方面发挥着重要作用。
DOI：
10.1172/jci.insight.124732
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发表时间：
2019
期刊：
影响因子：
8
通讯作者：
Gelman,AndrewE
中科院分区：
文献类型：
--
作者：
Liu,Zhiyi;Liao,Fuyi;Scozzi,Davide;Furuya,Yuka;Pugh,KaitlynN;Hachem,Ramsey;Chen,DelphineL;Cano,Marlene;Green,JonathanM;Krupnick,AlexanderS;Kreisel,Daniel;Perl,AnneKarinaT;Huang,HowardJ;Brody,StevenL;Gelman,AndrewE
Obliterative bronchiolitis (OB) is a poorly understood airway disease characterized by the generation of fibrotic bronchiolar occlusions. In the lung transplant setting, OB is a pathological manifestation of bronchiolitis obliterans syndrome (BOS), which is a major impediment to long-term recipient survival. Club cells play a key role in bronchiolar epithelial repair, but whether they promote lung transplant tolerance through preventing OB remains unclear. We determined if OB occurs in mouse orthotopic lung transplants following conditional transgene-targeted club cell depletion. In syngeneic lung transplants club cell depletion leads to transient epithelial injury followed by rapid club cell–mediated repair. In contrast, allogeneic lung transplants develop severe OB lesions that are largely devoid of club cells despite immunosuppression treatment. Lung allograft club cell ablation also triggers the recognition of alloantigens, and pulmonary restricted self-antigens reported associated with BOS development. However, CD8+ T cell depletion restores club cell reparative responses and prevents OB. In addition, ex vivo analysis reveals a specific role for alloantigen-primed CD8+ T cells in inhibiting club cell proliferation and maintenance. Taken together, our results demonstrate a vital role for club cells in maintaining lung transplant tolerance and propose a model to identify the underlying mechanisms of OB.
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影响因子：
3.7
作者：
De Vleeschauwer S;Jungraithmayr W;Wauters S;Willems S;Rinaldi M;Vaneylen A;Verleden S;Willems-Widyastuti A;Bracke K;Brusselle G;Verbeken E;Van Raemdonck D;Verleden G;Vanaudenaerde B
通讯作者：
Vanaudenaerde B
影响因子：
8.8
作者：
J. Salman;F. Ius;A. Knoefel;W. Sommer;T. Siemeni;Christian Kuehn;I. Tudorache;M. Avşar;Tomoyuki Nakagiri;G. Preissler;RA Hatz;M. Greer;Tobias Welte;A. Haverich;G. Warnecke
通讯作者：
J. Salman;F. Ius;A. Knoefel;W. Sommer;T. Siemeni;Christian Kuehn;I. Tudorache;M. Avşar;Tomoyuki Nakagiri;G. Preissler;RA Hatz;M. Greer;Tobias Welte;A. Haverich;G. Warnecke
DOI：
10.1152/ajplung.00169.2002
发表时间：
2002-12-01
影响因子：
4.9
作者：
You, YJ;Richer, EJ;Brody, SL
通讯作者：
Brody, SL
影响因子：
15.9
作者：
Burlingham, William J.;Love, Robert B.;Willkes, David S.
通讯作者：
Willkes, David S.
目前的免疫抑制方案未能充分抑制闭塞性细支气管炎综合征中 T 细胞颗粒酶 b 水平的升高
影响因子：
4.6
作者：
S. Hodge;G. Hodge;J. Ahern;C. Liew;Peter Hopkins;Daniel C. Chambers;P. Reynolds;M. Holmes
通讯作者：
M. Holmes