Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease
Abstract Castleman disease (CD) is a rare lymphoproliferative disorder. Among subtypes of CD, idiopathic multicentric CD-not otherwise specified (iMCD-NOS) has a poor prognosis and its pathogenesis is largely unknown. Here we present a xenotransplantation model of iMCD-NOS pathogenesis. Immunodefici...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42718-0 |
| _version_ | 1797636767508070400 |
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| author | Takuya Harada Yoshikane Kikushige Toshihiro Miyamoto Kazuko Uno Hiroaki Niiro Atsushi Kawakami Tomohiro Koga Koichi Akashi Kazuyuki Yoshizaki |
| author_facet | Takuya Harada Yoshikane Kikushige Toshihiro Miyamoto Kazuko Uno Hiroaki Niiro Atsushi Kawakami Tomohiro Koga Koichi Akashi Kazuyuki Yoshizaki |
| author_sort | Takuya Harada |
| collection | DOAJ |
| description | Abstract Castleman disease (CD) is a rare lymphoproliferative disorder. Among subtypes of CD, idiopathic multicentric CD-not otherwise specified (iMCD-NOS) has a poor prognosis and its pathogenesis is largely unknown. Here we present a xenotransplantation model of iMCD-NOS pathogenesis. Immunodeficient mice, transplanted with lymph node (LN) cells from iMCD-NOS patients, develop iMCD-like lethal inflammation, while mice transplanted with LN cells from non-iMCD patients without inflammation serve as negative control. Grafts depleted of human CD3+ T cells fail to induce inflammation in vivo. Upon engraftment, peripheral helper T (Tph) cells expand and levels of human CXCL13 substantially increase in the sera of mice. A neutralizing antibody against human CXCL13 blocks development of inflammation and improves survival in the recipient mice. Our study thus indicates that Tph cells, producing CXCL13 play a critical role in the pathogenesis of iMCD-NOS, and establishes iMCD-NOS as an immunoregulatory disorder. |
| first_indexed | 2024-03-11T12:39:50Z |
| format | Article |
| id | doaj.art-9f865d2680994d2498a4c67939139386 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T12:39:50Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9f865d2680994d2498a4c679391393862023-11-05T12:23:27ZengNature PortfolioNature Communications2041-17232023-10-0114111310.1038/s41467-023-42718-0Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman diseaseTakuya Harada0Yoshikane Kikushige1Toshihiro Miyamoto2Kazuko Uno3Hiroaki Niiro4Atsushi Kawakami5Tomohiro Koga6Koichi Akashi7Kazuyuki Yoshizaki8Department of Medicine and Biosystemic Science, Kyushu University Graduate School of MedicineDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of MedicineDepartment of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa UniversityLuis Pasteur Center for Medical ResearchDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of MedicineDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of MedicineThe Institute of Scientific and Industrial Research, SANKEN, Osaka UniversityAbstract Castleman disease (CD) is a rare lymphoproliferative disorder. Among subtypes of CD, idiopathic multicentric CD-not otherwise specified (iMCD-NOS) has a poor prognosis and its pathogenesis is largely unknown. Here we present a xenotransplantation model of iMCD-NOS pathogenesis. Immunodeficient mice, transplanted with lymph node (LN) cells from iMCD-NOS patients, develop iMCD-like lethal inflammation, while mice transplanted with LN cells from non-iMCD patients without inflammation serve as negative control. Grafts depleted of human CD3+ T cells fail to induce inflammation in vivo. Upon engraftment, peripheral helper T (Tph) cells expand and levels of human CXCL13 substantially increase in the sera of mice. A neutralizing antibody against human CXCL13 blocks development of inflammation and improves survival in the recipient mice. Our study thus indicates that Tph cells, producing CXCL13 play a critical role in the pathogenesis of iMCD-NOS, and establishes iMCD-NOS as an immunoregulatory disorder.https://doi.org/10.1038/s41467-023-42718-0 |
| spellingShingle | Takuya Harada Yoshikane Kikushige Toshihiro Miyamoto Kazuko Uno Hiroaki Niiro Atsushi Kawakami Tomohiro Koga Koichi Akashi Kazuyuki Yoshizaki Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease Nature Communications |
| title | Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease |
| title_full | Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease |
| title_fullStr | Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease |
| title_full_unstemmed | Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease |
| title_short | Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease |
| title_sort | peripheral helper t cell derived cxcl13 is a crucial pathogenic factor in idiopathic multicentric castleman disease |
| url | https://doi.org/10.1038/s41467-023-42718-0 |
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