BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis
IntroductionB-cell-activating factor (BAFF) is associated with donor-specific antibodies and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the effects of BAFF on T-cell physiological function have not been fully elucidated in...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.995149/full |
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| author | Youngwoo Jeon Youngwoo Jeon Youngwoo Jeon Jung-Yeon Lim Keon-Il Im Keon-Il Im Nayoun Kim Nayoun Kim Seok-Goo Cho Seok-Goo Cho Seok-Goo Cho Seok-Goo Cho |
| author_facet | Youngwoo Jeon Youngwoo Jeon Youngwoo Jeon Jung-Yeon Lim Keon-Il Im Keon-Il Im Nayoun Kim Nayoun Kim Seok-Goo Cho Seok-Goo Cho Seok-Goo Cho Seok-Goo Cho |
| author_sort | Youngwoo Jeon |
| collection | DOAJ |
| description | IntroductionB-cell-activating factor (BAFF) is associated with donor-specific antibodies and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the effects of BAFF on T-cell physiological function have not been fully elucidated in acute GVHD.MethodsWe examined the effects of belimumab, a monoclonal antibody targeting BAFF, for the treatment of acute GVHD. We examined the effects of T cells and B cells separately when inducing GVHD in mouse model.ResultsTherapeutic functional manipulation of endogenous BAFF can improve acute GVHD during the early post-transplant period. In this study, BAFF was shown to increase the proportions of CD4+IL-17+, CD4+IL-6+ Th17, and CD4+IFN-γ+ Th1 cells and to reduce the proportion of regulatory T (Treg) cells. Furthermore, the belimumab therapy group showed increased B220+IgD+IgM+ mature B cells but decreased B220+IgD−IgM− memory B cells, B220+Fas+GL-7+ germinal center formation, and B220+IgD−CD138+ plasma cells. These results indicate that BAFF can alleviate acute GVHD by simultaneously regulating T and B cells. Interestingly, the BAFF level was higher in patients with acute GVHD after HSCT compared with patients receiving chemotherapy.ConclusionThis study suggests that BAFF blockade might modulate CD4 +T-cell-induced acute GVHD early after allo-HSCT and the possibility of simultaneously controlling chronic GVHD, which may appear later after allo-HSCT. |
| first_indexed | 2024-04-11T13:38:17Z |
| format | Article |
| id | doaj.art-1a0041b127194f09943caeb9cb91cd4e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T13:38:17Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1a0041b127194f09943caeb9cb91cd4e2022-12-22T04:21:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.995149995149BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasisYoungwoo Jeon0Youngwoo Jeon1Youngwoo Jeon2Jung-Yeon Lim3Keon-Il Im4Keon-Il Im5Nayoun Kim6Nayoun Kim7Seok-Goo Cho8Seok-Goo Cho9Seok-Goo Cho10Seok-Goo Cho11Department of Hematology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLymphoma and Cell Therapy-Research Center, Yeouido St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaInstitute for Translational Research and Molecular Imaging, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedical Laboratory Science, Inje University, Kimhae, South KoreaInstitute for Translational Research and Molecular Imaging, The Catholic University of Korea, Seoul, South KoreaDepartment of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaInstitute for Translational Research and Molecular Imaging, The Catholic University of Korea, Seoul, South KoreaDepartment of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Hematology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLymphoma and Cell Therapy-Research Center, Yeouido St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaInstitute for Translational Research and Molecular Imaging, The Catholic University of Korea, Seoul, South KoreaDepartment of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaIntroductionB-cell-activating factor (BAFF) is associated with donor-specific antibodies and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the effects of BAFF on T-cell physiological function have not been fully elucidated in acute GVHD.MethodsWe examined the effects of belimumab, a monoclonal antibody targeting BAFF, for the treatment of acute GVHD. We examined the effects of T cells and B cells separately when inducing GVHD in mouse model.ResultsTherapeutic functional manipulation of endogenous BAFF can improve acute GVHD during the early post-transplant period. In this study, BAFF was shown to increase the proportions of CD4+IL-17+, CD4+IL-6+ Th17, and CD4+IFN-γ+ Th1 cells and to reduce the proportion of regulatory T (Treg) cells. Furthermore, the belimumab therapy group showed increased B220+IgD+IgM+ mature B cells but decreased B220+IgD−IgM− memory B cells, B220+Fas+GL-7+ germinal center formation, and B220+IgD−CD138+ plasma cells. These results indicate that BAFF can alleviate acute GVHD by simultaneously regulating T and B cells. Interestingly, the BAFF level was higher in patients with acute GVHD after HSCT compared with patients receiving chemotherapy.ConclusionThis study suggests that BAFF blockade might modulate CD4 +T-cell-induced acute GVHD early after allo-HSCT and the possibility of simultaneously controlling chronic GVHD, which may appear later after allo-HSCT.https://www.frontiersin.org/articles/10.3389/fimmu.2022.995149/fullgraft-versus-host diseasehematopoietic stem cell transplantationB-cell-activating factor (BAFF)belimumabregulatory T-lymphocytes |
| spellingShingle | Youngwoo Jeon Youngwoo Jeon Youngwoo Jeon Jung-Yeon Lim Keon-Il Im Keon-Il Im Nayoun Kim Nayoun Kim Seok-Goo Cho Seok-Goo Cho Seok-Goo Cho Seok-Goo Cho BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis Frontiers in Immunology graft-versus-host disease hematopoietic stem cell transplantation B-cell-activating factor (BAFF) belimumab regulatory T-lymphocytes |
| title | BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis |
| title_full | BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis |
| title_fullStr | BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis |
| title_full_unstemmed | BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis |
| title_short | BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis |
| title_sort | baff blockade attenuates acute graft versus host disease directly via the dual regulation of t and b cell homeostasis |
| topic | graft-versus-host disease hematopoietic stem cell transplantation B-cell-activating factor (BAFF) belimumab regulatory T-lymphocytes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.995149/full |
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