Interleukin 21 blockade modulates activated T- and B-cell homeostasis via B-cell activating factor pathway-mediated inhibition in a murine model of acute graft-versus-host disease.

Autor: Lim JY; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea., Park MJ; Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea., Im KI; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea., Kim N; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea., Park HS; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea., Lee SH; Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea., Kim EK; Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea., Nam YS; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea., Lee ES; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea., Cho ML; Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea., Cho SG; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea. Electronic address: chosg@catholic.ac.kr.
Jazyk: angličtina
Zdroj: Experimental hematology [Exp Hematol] 2015 Jan; Vol. 43 (1), pp. 23-31.e1-2. Date of Electronic Publication: 2014 Sep 20.
DOI: 10.1016/j.exphem.2014.09.005
Abstrakt: Interleukin (IL) 21 plays a key role in the development of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. Therapeutic manipulation of IL-21 activity may improve acute GVHD during the early-posttransplant period. We investigated the mechanisms regulating T- and B-cells during IL-21 blockade in acute GVHD. Interleukin 21 blockade enhanced regulatory T and T helper (Th) 2 cell differentiation and inhibited Th1- and Th17-derived transcription factors and cytokines as a modulator of activated T-cells. Interleukin 21(-/-) cell recipients showed increased mature B- and marginal-zone B-cells, but decreased memory B-cells, germinal center formation, and plasma cells that did not lead to immunoglobulin production. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in the induction and maintenance of T- and B-cell responses. We observed decreased levels of only BAFF during acute GVHD and confirmed that mammalian target of rapamycin complex 1 was reduced by the BAFF/BAFF-receptor pathway. Therefore, this study suggests that IL-21 blockade modulates activated T- and B-cell homeostasis via BAFF-pathway-mediated inhibition in acute GVHD following murine allogeneic bone marrow transplantation.
(Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: