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Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease

Author

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  • Takuya Harada

    (Kyushu University Graduate School of Medicine)

  • Yoshikane Kikushige

    (Kyushu University Graduate School of Medicine
    Kyushu University Hospital)

  • Toshihiro Miyamoto

    (Kanazawa University)

  • Kazuko Uno

    (Luis Pasteur Center for Medical Research)

  • Hiroaki Niiro

    (Kyushu University Graduate School of Medicine)

  • Atsushi Kawakami

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Tomohiro Koga

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Koichi Akashi

    (Kyushu University Graduate School of Medicine
    Kyushu University Hospital)

  • Kazuyuki Yoshizaki

    (Osaka University
    Medical corporation of Tokushukai)

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.

Suggested Citation

  • Takuya Harada & Yoshikane Kikushige & Toshihiro Miyamoto & Kazuko Uno & Hiroaki Niiro & Atsushi Kawakami & Tomohiro Koga & Koichi Akashi & Kazuyuki Yoshizaki, 2023. "Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42718-0
    DOI: 10.1038/s41467-023-42718-0
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    1. Sheila K. Pierson & Laura Katz & Reece Williams & Melanie Mumau & Michael Gonzalez & Stacy Guzman & Ayelet Rubenstein & Ana B. Oromendia & Philip Beineke & Alexander Fosså & Frits van Rhee & David C. , 2022. "CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Deepak A. Rao & Michael F. Gurish & Jennifer L. Marshall & Kamil Slowikowski & Chamith Y. Fonseka & Yanyan Liu & Laura T. Donlin & Lauren A. Henderson & Kevin Wei & Fumitaka Mizoguchi & Nikola C. Tesl, 2017. "Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis," Nature, Nature, vol. 542(7639), pages 110-114, February.
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