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. 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 inflam

SUBMITTER: Harada T 

PROVIDER: S-EPMC10618253 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature