Hengcheng Zhang1, Peter T Sage. 1. Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Antibody-mediated rejection (AbMR) after solid organ transplantation is tightly controlled by multiple cells of the immune system. Tfh and Tfr cells are essential controllers of antibody responses making them putative targets for therapeutics. However, the mechanisms of how Tfh and Tfr cells regulate B cell and antibody responses are not completely understood. Here, we summarize recent studies elucidating the functions of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells as well as their possible roles in regulating AbMR in solid organ transplantation. RECENT FINDINGS: New tools have been developed to study the roles of Tfh and Tfr cells in specific disease states, including AbMR after solid organ transplantation. These tools suggest complex roles for Tfh and Tfr cells in controlling antibody responses. Nevertheless, studies in solid organ transplant rejection suggest that Tfh and Tfr cells may be high value targets for therapeutics. However, specific strategies to target these cells are still being investigated. SUMMARY: AbMR is still a substantial clinical problem that restricts long-term survival after solid organ transplantation. Growing evidence has demonstrated a pivotal role for Tfh and Tfr cells in controlling AbMR. In addition to providing an early indication of rejection as a biomarker, targeting Tfh and Tfr cells as a therapeutic strategy offers new hope for alleviating AbMR.
PURPOSE OF REVIEW: Antibody-mediated rejection (AbMR) after solid organ transplantation is tightly controlled by multiple cells of the immune system. Tfh and Tfr cells are essential controllers of antibody responses making them putative targets for therapeutics. However, the mechanisms of how Tfh and Tfr cells regulate B cell and antibody responses are not completely understood. Here, we summarize recent studies elucidating the functions of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells as well as their possible roles in regulating AbMR in solid organ transplantation. RECENT FINDINGS: New tools have been developed to study the roles of Tfh and Tfr cells in specific disease states, including AbMR after solid organ transplantation. These tools suggest complex roles for Tfh and Tfr cells in controlling antibody responses. Nevertheless, studies in solid organ transplant rejection suggest that Tfh and Tfr cells may be high value targets for therapeutics. However, specific strategies to target these cells are still being investigated. SUMMARY: AbMR is still a substantial clinical problem that restricts long-term survival after solid organ transplantation. Growing evidence has demonstrated a pivotal role for Tfh and Tfr cells in controlling AbMR. In addition to providing an early indication of rejection as a biomarker, targeting Tfh and Tfr cells as a therapeutic strategy offers new hope for alleviating AbMR.
Authors: Rodrigo Benedetti Gassen; Thiago J Borges; María José Pérez-Sáez; Hengcheng Zhang; Ayman Al Jurdi; Laura Llinàs-Mallol; Bruno Aoyama; Maurício Lima; Julio Pascual; Peter T Sage; Naoka Murakami; Leonardo V Riella Journal: Am J Transplant Date: 2022-04-15 Impact factor: 9.369
Authors: Yisi Lu; Roy Jiang; Alec W Freyn; Jiawei Wang; Shirin Strohmeier; Katlyn Lederer; Michela Locci; Hongyu Zhao; Davide Angeletti; Kevin C O'Connor; Steven H Kleinstein; Raffael Nachbagauer; Joe Craft Journal: J Exp Med Date: 2021-03-01 Impact factor: 14.307
Authors: Michael L Dixon; Lin Luo; Sadashib Ghosh; Jeffrey M Grimes; Jonathan D Leavenworth; Jianmei W Leavenworth Journal: Mol Cancer Date: 2021-11-20 Impact factor: 27.401
Authors: Cecilia B Cavazzoni; Benjamin L Hanson; Manuel A Podestà; Elsa D Bechu; Rachel L Clement; Hengcheng Zhang; Joe Daccache; Tamara Reyes-Robles; Erik C Hett; Kalpit A Vora; Olugbeminiyi O Fadeyi; Rob C Oslund; Daria J Hazuda; Peter T Sage Journal: Cell Rep Date: 2022-02-01 Impact factor: 9.423
Authors: Elizabeth F Wallin; Elaine C Jolly; Ondřej Suchánek; J Andrew Bradley; Marion Espéli; David R W Jayne; Michelle A Linterman; Kenneth G C Smith Journal: Blood Date: 2014-09-15 Impact factor: 22.113
Authors: Chiara Guglielmo; Sofia Bin; Chiara Cantarelli; Susan Hartzell; Andrea Angeletti; Chiara Donadei; Arun Cumpelik; Lisa Anderson; Evan Cody; Peter T Sage; Gaetano La Manna; Enrico Fiaccadori; Peter S Heeger; Paolo Cravedi Journal: J Am Soc Nephrol Date: 2021-07-14 Impact factor: 14.978