Rapamycin Prevents Bronchiolitis Obliterans Through Increasing Regulatory B Cells Infiltration in A Murine Tracheal Transplantation Model Yunge Zhao, Jacob.

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Presentation transcript:

Rapamycin Prevents Bronchiolitis Obliterans Through Increasing Regulatory B Cells Infiltration in A Murine Tracheal Transplantation Model Yunge Zhao, Jacob R. Gillen, Akshaya K. Meher, Jordan A. Burns, David A. Harris, Irving L. Kron, and Christine L. Lau* Department of Surgery, University of Virginia Health System, Charlottesville, Virginia. * Corresponding Author

Presenter Disclosure Yunge Zhao The following relationships exist related to this presentation: This study is supported by The Advancing Research in Transplantation Science (ARTS) 2011 Grant Program from Pfizer

Introduction ? Cellular Infiltration Rapamycin Recruitment of Fibrocytes Ann Thorac Surg. 2013 95(5):1768-75. Cellular Infiltration Epithelial Progenitor Cells Ann Thorac Surg. 2013, 96(2):464-72 ? Bronchiolitis Obliterans

Regulatory B Cells/Bregs Bregs secrete IL-10 and TGF-beta1. IgM+ but IgG- B cells.

Min Yang et al. Cell Mol Immunol 10: 122-132, 2013.

Mouse Heterotopic Tracheal Transplantation (HTT) Model Donor: Balb/c (BC), MHC class I Recipient: C57BL/6 (B6), MHC class II H-2d H-2b Allografts:

Experimental Design Mouse HTT Model: Isograft controls Experimental Allograft+DMSO Groups Allograft+Rapamycin 5mg/kg/day (n=6) Allograft+Rapamycin 10mg/kg/day * DMSO and Rapamycin was diluted in saline and IP 2. Luminex Assays of Cytokines and Growth Factors: 3. Immunohistochemistry and Densitometric Analysis:

Effects of Rapamycin on Luminal Obliteration in a mouse HTT Model

Increasing of Cellular Infiltration Post Rapamycin Treatment

Identifying the Infiltrated Cells

Rapamycin Treatment Significantly Increased B Cells Infiltration

IgM+ & IgG- B220+, IL-10+ & TGF-b1+

IL-10 & TGFb1

Treatment with Rapamycin Significantly Increased IL-10 and IL-4 Production in Allografts

Treatment with Rapamycin Markedly Increased Foxp3+ Treg Cells in the Allografts

Summary Rapamycin Bregs Tregs Foxp3+ Bronchiolitis Obliterans B220+IL-10+TGFβ1+IgM+IgG- Tregs Foxp3+ IL-10/TGFb1

Thank you !