Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation.

Autor:	Zeng F; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Department of Dermatology and Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.; The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China., Chen Z; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.; The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.; Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center, Institute of Hepatobiliary Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, China., Chen R; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Department of Kidney Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China., Shufesky WJ; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA., Bandyopadhyay M; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Camirand G; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Oberbarnscheidt MH; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Sullivan MLG; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Baty CJ; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, PA 15261, USA., Yang MQ; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA., Calderon M; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Stolz DB; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Erdos G; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Pelanda R; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Brennan TV; Cedars-Sinai Comprehensive Transplant Center, Los Angeles, CA 90048, USA., Catz SD; The Scripps Research Institute, La Jolla, CA 92037, USA., Watkins SC; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA., Larregina AT; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Morelli AE; T.E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA. morelli@pitt.edu.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2021 Mar 17; Vol. 13 (585).
DOI:	10.1126/scitranslmed.abb0122
Abstrakt:	Despite the role of donor-specific antibodies (DSAs) in recognizing major histocompatibility complex (MHC) antigens and mediating transplant rejection, how and where recipient B cells in lymphoid tissues encounter donor MHC antigens remains unclear. Contrary to the dogma, we demonstrated here that migration of donor leukocytes out of skin or heart allografts is not necessary for B or T cell allosensitization in mice. We found that mouse skin and cardiac allografts and human skin grafts release cell-free donor MHC antigens via extracellular vesicles (EVs) that are captured by subcapsular sinus (SCS) macrophages in lymph nodes or analog macrophages in the spleen. Donor EVs were transported across the SCS macrophages, and donor MHC molecules on the EVs were recognized by alloreactive B cells. This triggered B cell activation and DSA production, which were both prevented by SCS macrophage depletion. These results reveal an unexpected role for graft-derived EVs and open venues to interfere with EV biogenesis, trafficking, or function to restrain priming or reactivation of alloreactive B cells. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu