Background: Obstructive bronchiolitis (OB) characterized by chronic rejection, is the main complication after lung transplantation which limits the long-term survival of the recipients. Innate immune responses have been shown to contribute to the development of OB. In this study, a murine heterotopic tracheal transplantation model was used and treated with a novel innate immune inhibitor, MyD88 inhibitor TJ-M2010-5.

Methods: Syngeneic tracheal grafts were transplanted heterotopically from C57BL/6 mice to C57BL/6 mice as model control. Allografts from BALB/c mice were transplanted to C57BL/6 mice. The allograft recipients were treated with/without the inhibitor alone and plus anti-mouse CD154 (MR-1). The grafts were harvested at 7, 14 and 28 days for histological and real-time RT-PCR analyses.

Results: In non-treatment group, almost all the epithelial membrane of the tracheal grafts fell off at 7 day, and tracheal occlusion reached its peak at 28 day. However, the loss of the epithelium and the obstructionof the airway were significantly improved in mice treated with TJ-M2010-5 plus MR-1 – i.e. – i.e. . The relative mRNA expressions of pro-inflammatory cytokines were upregulated in allogeneic tracheal grafts, whereas the treated grafts by the two agents apparently reduced the production of pro-inflammatory cytokines and infiltration of inflammatory cells.

Conclusions: In heterotopic tracheal transplantation model, TJ-M2010-5 combined with MR1 could ameliorate the development of obstructive bronchiolitis.

Key words: MyD88; heterotopic tracheal transplantation; obstructive bronchiolitis.

CITATION INFORMATION: Yang M, Zhang X, Chen G, Ding Z.-C, Miao Y, Yang Y, Zhou P. A Novel MyD88 Inhibitor Attenuates Allograft Rejection in Heterotopic Tracheal Transplantation in Mice. Am J Transplant. 2017;17 (suppl 3).

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