CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-Disease
Development of Graft Versus Host Disease (GVHD) represents a major impediment in allogeneic hematopoietic stem cell transplantation (HSCT). The observation that the presence of bone marrow and circulating hematogones correlated with reduced GVHD risks prompted us to evaluate whether B-cell progenito...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.790564/full |
| _version_ | 1811271878643286016 |
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| author | Viviane A. Agbogan Pauline Gastineau Emmanuel Tejerina Saoussen Karray Flora Zavala |
| author_facet | Viviane A. Agbogan Pauline Gastineau Emmanuel Tejerina Saoussen Karray Flora Zavala |
| author_sort | Viviane A. Agbogan |
| collection | DOAJ |
| description | Development of Graft Versus Host Disease (GVHD) represents a major impediment in allogeneic hematopoietic stem cell transplantation (HSCT). The observation that the presence of bone marrow and circulating hematogones correlated with reduced GVHD risks prompted us to evaluate whether B-cell progenitors, which provide protection in various autoimmune disease models following activation with the TLR-9 agonist CpG (CpG-proBs), could likewise reduce this allogeneic disorder. In a murine model of GVHD that recapitulates an initial phase of acute GVHD followed by a phase of chronic sclerodermatous GVHD, we found that CpG-proBs, adoptively transferred during the initial phase of disease, reduced the diarrhea score and mostly prevented cutaneous fibrosis. Progenitors migrated to the draining lymph nodes and to the skin where they mainly differentiated into follicular B cells. CpG activation and IFN-γ expression were required for the protective effect, which resulted in reduced CD4+ T-cell-derived production of critical cytokines such as TGF-β, IL-13 and IL-21. Adoptive transfer of CpG-proBs increased the T follicular regulatory to T follicular helper (Tfr/Tfh) ratio. Moreover, CpG-proBs privileged the accumulation of IL-10-positive CD8+ T cells, B cells and dendritic cells in the skin. However, CpG-proBs did not improve survival. Altogether, our findings support the notion that adoptively transferred CpG-proBs exert immunomodulating effect that alleviates symptoms of GVHD but require additional anti-inflammatory strategy to improve survival. |
| first_indexed | 2024-04-12T22:30:08Z |
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| id | doaj.art-fbd5e8ae4aee49459eed7748c803198a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T22:30:08Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fbd5e8ae4aee49459eed7748c803198a2022-12-22T03:14:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.790564790564CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-DiseaseViviane A. Agbogan0Pauline Gastineau1Emmanuel Tejerina2Saoussen Karray3Flora Zavala4Université Paris Cité, INSERM U1151, CNRS UMR8152, Institut Necker Enfants Malades (INEM), Paris, FranceUniversité Paris Cité, INSERM U1151, CNRS UMR8152, Institut Necker Enfants Malades (INEM), Paris, FranceUniversité Paris Cité, INSERM U1151, CNRS UMR8152, Institut Necker Enfants Malades (INEM), Paris, FranceUniversité Paris Cité, INSERM U976, Institut de Recherche Saint-Louis (IRSL), Hôpital Saint-Louis, Paris, FranceUniversité Paris Cité, INSERM U1151, CNRS UMR8152, Institut Necker Enfants Malades (INEM), Paris, FranceDevelopment of Graft Versus Host Disease (GVHD) represents a major impediment in allogeneic hematopoietic stem cell transplantation (HSCT). The observation that the presence of bone marrow and circulating hematogones correlated with reduced GVHD risks prompted us to evaluate whether B-cell progenitors, which provide protection in various autoimmune disease models following activation with the TLR-9 agonist CpG (CpG-proBs), could likewise reduce this allogeneic disorder. In a murine model of GVHD that recapitulates an initial phase of acute GVHD followed by a phase of chronic sclerodermatous GVHD, we found that CpG-proBs, adoptively transferred during the initial phase of disease, reduced the diarrhea score and mostly prevented cutaneous fibrosis. Progenitors migrated to the draining lymph nodes and to the skin where they mainly differentiated into follicular B cells. CpG activation and IFN-γ expression were required for the protective effect, which resulted in reduced CD4+ T-cell-derived production of critical cytokines such as TGF-β, IL-13 and IL-21. Adoptive transfer of CpG-proBs increased the T follicular regulatory to T follicular helper (Tfr/Tfh) ratio. Moreover, CpG-proBs privileged the accumulation of IL-10-positive CD8+ T cells, B cells and dendritic cells in the skin. However, CpG-proBs did not improve survival. Altogether, our findings support the notion that adoptively transferred CpG-proBs exert immunomodulating effect that alleviates symptoms of GVHD but require additional anti-inflammatory strategy to improve survival.https://www.frontiersin.org/articles/10.3389/fimmu.2022.790564/fullallogeneic stem cell transplantation (allo-SCT)regulatory B-cell progenitorsCpG-proBscell therapyfibrosisBregs: regulatory B cells |
| spellingShingle | Viviane A. Agbogan Pauline Gastineau Emmanuel Tejerina Saoussen Karray Flora Zavala CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-Disease Frontiers in Immunology allogeneic stem cell transplantation (allo-SCT) regulatory B-cell progenitors CpG-proBs cell therapy fibrosis Bregs: regulatory B cells |
| title | CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-Disease |
| title_full | CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-Disease |
| title_fullStr | CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-Disease |
| title_full_unstemmed | CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-Disease |
| title_short | CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine Graft-Versus-Host-Disease |
| title_sort | cpg activated regulatory b cell progenitors alleviate murine graft versus host disease |
| topic | allogeneic stem cell transplantation (allo-SCT) regulatory B-cell progenitors CpG-proBs cell therapy fibrosis Bregs: regulatory B cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.790564/full |
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