Date: Tuesday, June 14, 2016
Session Name: Concurrent Session: Allograft Tolerance 2: Animal Models
Session Time: 2:30pm-4:00pm
Presentation Time: 2:42pm-2:54pm
Location: Room 309
Introduction: The TAM (Tyro3, Axl and Mer) receptor tyrosine kinases (RTKs) mediate homeostatic phagocytosis of apoptotic cells, and transmit regulatory signals that modulate immune response. Currently, their role in transplant tolerance is unknown.
Methods: In this study, we address the role of Mer in transplant tolerance in a BALB/c à B6 heart transplant model in which tolerance is induced by recipient treatment with donor splenocytes (SP) treated with 1-ehtyl-3-(3-dimethylaminopropyl) carbodiimide (ECDI).
Results: While baseline expression of Mer was primarily only detected on the red pulp macrophages, recipient mice treated with donor ECDI-SP significantly up-regulated Mer expression on both the CD68+SIGN-R1+ marginal zone macrophages and CD68+CD169+ metalophilic macrophages. This up-regulation was most prominent in macrophages that had phagocytosed the injected donor ECDI-SP. To determine the role of Mer in mediating transplant tolerance by donor ECDI-SP, we utilized Mer-/- mice. Bone marrow derived macrophages (BMDM) from Mer-/- and Mer+/+ were cultured with allogeneic ECDI-SP. While Mer+/+ BMDM exhibited marked up-regulation of M-CSF and essentially completely inhibited expressions of IFN-g and TNF-a following culturing with allogeneic ECDI-SP, Mer-/- BMDM exhibited an opposite pattern, i.e. inhibited up-regulation of M-CSF but marked up-regulation of IFN-g. This altered pattern of expressions of M-CSF and inflammatory cytokines correlated with an absence of the expansion of myeloid derived suppressor cells (MDSCs) that were otherwise induced in recipients treated by donor ECDI-SP. Consistent with a critical role of Mer signaling in the induction of transplant tolerance, recipient Mer deficiency completely abolished allograft protection provided by donor ECDI-SP.
Conclusion: The receptor tyrosine kinase Mer plays a critical role in tolerogenic signaling in splenic macrophages, MDSC expansion, and consequently in the induction of transplantation tolerance.
CITATION INFORMATION: Zhang L, DeBerge M, Zhang X, Wang J, Zhang Z, Thorp E, Luo X. Receptor Tyrosine Kinase Mer Mediates Expansion of MDSCs Critical for Transplantation Tolerance. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Zhang L, DeBerge M, Zhang X, Wang J, Zhang Z, Thorp E, Luo X. Receptor Tyrosine Kinase Mer Mediates Expansion of MDSCs Critical for Transplantation Tolerance. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/receptor-tyrosine-kinase-mer-mediates-expansion-of-mdscs-critical-for-transplantation-tolerance/. Accessed March 3, 2021.
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