Anti-inflammatory role of APRIL by modulating regulatory B cells in antigen-induced arthritis

PLoS One. 2024 May 1;19(5):e0292028. doi: 10.1371/journal.pone.0292028. eCollection 2024.

Abstract

APRIL (A Proliferation-Inducing Ligand), a member of the TNF superfamily, was initially described for its ability to promote proliferation of tumor cells in vitro. Moreover, this cytokine has been related to the pathogenesis of different chronic inflammatory diseases, such as rheumatoid arthritis. This study aimed to evaluate the ability of APRIL in regulating B cell-mediated immune response in the antigen-induced arthritis (AIA) model in mice. AIA was induced in previously immunized APRIL-transgenic (Tg) mice and their littermates by administration of antigen (mBSA) into the knee joints. Different inflammatory cell populations in spleen and draining lymph nodes were analyzed using flow cytometry and the assay was performed in the acute and chronic phases of the disease, while cytokine levels were assessed by ELISA. In the acute AIA, APRIL-Tg mice developed a less severe condition and a smaller inflammatory infiltrate in articular tissues when compared with their littermates. We also observed that the total cellularity of draining lymph nodes was decreased in APRIL-Tg mice. Flow cytometry analysis revealed an increase of CD19+IgM+CD5+ cell population in draining lymph nodes and an increase of CD19+CD21hiCD23hi (B regulatory) cells in APRIL-Tg mice with arthritis as well as an increase of IL-10 and CXCL13 production in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental* / immunology
  • Arthritis, Experimental* / pathology
  • B-Lymphocytes, Regulatory* / immunology
  • Interleukin-10 / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Transgenic*
  • Spleen / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13* / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13* / metabolism

Substances

  • Interleukin-10
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tnfsf13 protein, mouse

Grants and funding

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) https://www.cnpq.br (DV-V Grants: 482028/2009-2 and 305927/2010-8); Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) – https://www.faperj.br (ACS Grant: E-26/102.500/2010). The study was also supported by a grant from MercoSur https://www.mercosur.int through the Fund for Structural Convergence (FOCEM); by intramural funds from Oswaldo Cruz Foundation (Fiocruz) www.fiocruz.br and from Fluminense Federal University (UFF) https://www.uff.br. There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.