Rapamycin Prevents Bronchiolitis Obliterans Rapamycin Prevents Bronchiolitis Obliterans Through Increasing Regulatory B Cells Through Increasing Regulatory B Cells
Infiltration in A Murine Tracheal Infiltration in A Murine Tracheal Transplantation ModelTransplantation Model
Yunge Zhao, Jacob R. Gillen, Akshaya K. Meher, Jordan A. Burns, David A. Yunge Zhao, Jacob R. Gillen, Akshaya K. Meher, Jordan A. Burns, David A. Harris, Irving L. Kron, and Christine L. Lau*Harris, Irving L. Kron, and Christine L. Lau*
Department of Surgery, University of Virginia Health System, Charlottesville, Virginia. Department of Surgery, University of Virginia Health System, Charlottesville, Virginia.
* Corresponding Author* Corresponding Author
Presenter DisclosurePresenter Disclosure
Yunge ZhaoYunge Zhao
The following relationships exist related The following relationships exist related to this presentation:to this presentation:
This study is supported by This study is supported by The The Advancing Research in Transplantation Advancing Research in Transplantation Science (ARTS) 2011 Grant Program Science (ARTS) 2011 Grant Program from Pfizerfrom Pfizer
IntroductionRapamycin
Epithelial Epithelial Progenitor CellsProgenitor CellsAnn Thorac Surg. 2013, Ann Thorac Surg. 2013, 96(2):464-7296(2):464-72
Recruitment of Recruitment of FibrocytesFibrocytes Ann Ann Thorac Surg. 2013 Thorac Surg. 2013 95(5):1768-7595(5):1768-75..
Bronchiolitis Obliterans Bronchiolitis Obliterans
Cellular Infiltration
?
Regulatory B Cells/BregsRegulatory B Cells/Bregs
B220+ B220+
Bregs secrete IL-10 and TGF-beta1. Bregs secrete IL-10 and TGF-beta1.
IgM+ but IgG- B cells. IgM+ but IgG- B cells.
Min Yang et al. Cell Mol Immunol 10: 122-132, 2013.
Mouse Heterotopic Tracheal Mouse Heterotopic Tracheal Transplantation (HTT) Model Transplantation (HTT) Model
Donor: Balb/c (BC), MHC class I Donor: Balb/c (BC), MHC class I
Recipient: C57BL/6 (B6), MHC class IIRecipient: C57BL/6 (B6), MHC class II
Allografts:
H-2d H-2b
Experimental Design
2. Luminex Assays of Cytokines and Growth Factors: 3. Immunohistochemistry and Densitometric Analysis:
1. 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
Effects of Rapamycin on Luminal Obliteration in a mouse HTT Model
Increasing of Cellular InfiltrationPost Rapamycin Treatment
Identifying the Infiltrated Cells
Rapamycin Treatment Significantly Increased B Cells Infiltration
IgM+ & IgG-
B220+, IL-10+ & TGF-
IL-10 & TGF1
Treatment with RapamycinSignificantly Increased IL-10 and IL-4 Production in Allografts
Treatment with Rapamycin Markedly Increased Foxp3+ Treg Cells in the Allografts
Summary
Rapamycin
Bronchiolitis Obliterans Bronchiolitis Obliterans
BregsB220+IL-10+TGFβ1+IgM+IgG-
Tregs Foxp3+
IL-10/TGF
Thank you !
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