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BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis
INTRODUCTION: B-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 i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763883/ https://www.ncbi.nlm.nih.gov/pubmed/36561743 http://dx.doi.org/10.3389/fimmu.2022.995149 |
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author | Jeon, Youngwoo Lim, Jung-Yeon Im, Keon-Il Kim, Nayoun Cho, Seok-Goo |
author_facet | Jeon, Youngwoo Lim, Jung-Yeon Im, Keon-Il Kim, Nayoun Cho, Seok-Goo |
author_sort | Jeon, Youngwoo |
collection | PubMed |
description | INTRODUCTION: B-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. METHODS: We 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. RESULTS: Therapeutic 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. CONCLUSION: This 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. |
format | Online Article Text |
id | pubmed-9763883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97638832022-12-21 BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis Jeon, Youngwoo Lim, Jung-Yeon Im, Keon-Il Kim, Nayoun Cho, Seok-Goo Front Immunol Immunology INTRODUCTION: B-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. METHODS: We 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. RESULTS: Therapeutic 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. CONCLUSION: This 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. Frontiers Media S.A. 2022-12-06 /pmc/articles/PMC9763883/ /pubmed/36561743 http://dx.doi.org/10.3389/fimmu.2022.995149 Text en Copyright © 2022 Jeon, Lim, Im, Kim and Cho https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Jeon, Youngwoo Lim, Jung-Yeon Im, Keon-Il Kim, Nayoun Cho, Seok-Goo BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis |
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 | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763883/ https://www.ncbi.nlm.nih.gov/pubmed/36561743 http://dx.doi.org/10.3389/fimmu.2022.995149 |
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