title: 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.
abstract: 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.
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Keon-Il
authors.initials: KI
authors.lastname: Im
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Nayoun
authors.initials: N
authors.lastname: Kim
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Hyun-Sil
authors.initials: HS
authors.lastname: Park
authors.affiliation: Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea.
authors.forename: Eun-Kung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Nam
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Eun-Sol
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.affiliation: 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.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D000208:Acute Disease; D000818:Animals; D053264:B-Cell Activating Factor / Q000096:biosynthesis / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D017690:Cell Transplantation; D005786:Gene Expression Regulation / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D006706:Homeostasis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D038041:Lymphopoiesis; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors; D010950:Plasma Cells / Q000276:immunology; D011828:Radiation Chimera; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000502:physiology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000096:biosynthesis / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D053264:B-Cell Activating Factor; D007378:Interleukins; D046912:Multiprotein Complexes; C114631:TNFSF13 protein, human; C505720:Tnfsf13b protein, mouse; D014157:Transcription Factors; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D007371:Interferon-gamma; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D000098546:Interleukin-21