IL-21-producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts.

Autor: Zhang H; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Cavazzoni CB; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Podestà MA; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Bechu ED; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Ralli G; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chandrakar P; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lee JM; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sayin I; Department of Surgery, Section of Transplantation, University of Chicago, Chicago, Illinois, USA., Tullius SG; Division of Transplant Surgery & Transplant Surgery Research Laboratory, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Abdi R; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chong AS; Department of Surgery, Section of Transplantation, University of Chicago, Chicago, Illinois, USA., Blazar BR; Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular Therapies, University of Minnesota, Minneapolis, Minnesota, USA., Sage PT; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2023 Oct 23; Vol. 8 (20). Date of Electronic Publication: 2023 Oct 23.
DOI: 10.1172/jci.insight.169793
Abstrakt: Follicular helper T (Tfh) cells have been implicated in controlling rejection after allogeneic kidney transplantation, but the precise subsets, origins, and functions of Tfh cells in this process have not been fully characterized. Here we show that a subset of effector Tfh cells marked by previous IL-21 production is potently induced during allogeneic kidney transplantation and is inhibited by immunosuppressive agents. Single-cell RNA-Seq revealed that these lymph node (LN) effector Tfh cells have transcriptional and clonal overlap with IL-21-producing kidney-infiltrating Tfh cells, implicating common origins and developmental trajectories. To investigate the precise functions of IL-21-producing effector Tfh cells in LNs and allografts, we used a mouse model to selectively eliminate these cells and assessed allogeneic B cell clonal dynamics using a single B cell culture system. We found that IL-21-producing effector Tfh cells were essential for transplant rejection by regulating donor-specific germinal center B cell clonal dynamics both systemically in the draining LN and locally within kidney grafts. Thus, IL-21-producing effector Tfh cells have multifaceted roles in Ab-mediated rejection after kidney transplantation by promoting B cell alloimmunity.
Databáze: MEDLINE
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