1. 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

2. 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

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

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

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

6. 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:

7. 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:

8. Effects of Rapamycin on Luminal Obliteration
in a mouse HTT Model

9. Increasing of Cellular Infiltration Post Rapamycin Treatment

10. Identifying the Infiltrated Cells

11. Rapamycin Treatment
Significantly Increased B Cells Infiltration

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

13. IL-10 & TGFb1

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

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

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

17. Thank you !