IL-33-primed human mast cells drive IL-9 production by CD4+ effector T cells in an OX40L-dependent manner

Front Immunol. 2024 Oct 2:15:1470546. doi: 10.3389/fimmu.2024.1470546. eCollection 2024.

Abstract

Interleukin-33 (IL-33) is an alarmin released by epithelial cells in response to tissue damage. It activates resident immune sentinel cells, which then produce signals commonly associated with type 2 immune responses, particularly affecting infiltrating antigen-specific T cells. Given that mast cells (MCs) are a primary target of IL-33 and can shape T helper (Th) cell responses, we investigated the effect of IL-33 priming on the ability of MCs to influence Th cell cytokine production. To examine the Th cell/MC interaction, we developed human primary MC/memory CD4+ T-cell coculture systems involving both cognate and non-cognate interactions. Our results demonstrated that IL-33-primed MCs, whether as bystander cells cocultured with activated effector T cells or functioning as antigen-presenting cells, promoted IL-9 and increased IL-13 production in Th cells via an OX40L-dependent mechanism. This indicates that MCs sense IL-33-associated danger, prompting them to direct Th cells to produce the key type 2 effector cytokines IL-9 and IL-13.

Keywords: IL-33; IL-9; OX40L; Th cell; mast cell.

MeSH terms

  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Humans
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Interleukin-33* / immunology
  • Interleukin-9* / metabolism
  • Lymphocyte Activation / immunology
  • Mast Cells* / immunology
  • Mast Cells* / metabolism
  • OX40 Ligand* / metabolism

Substances

  • Interleukin-33
  • Interleukin-9
  • OX40 Ligand
  • IL9 protein, human
  • IL33 protein, human
  • TNFSF4 protein, human
  • Interleukin-13

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Laboratoire d’Excellence Toulouse Cancer (TOUCAN) (contract ANR11-LABEX) and from the Ligue Nationale contre le Cancer (Equipe labellisée 2018). EL was supported by fellowships from the French Ministry of Education and Research and from Ligue Nationale contre le Cancer. NC is a recipient of the grant from ANR (ANR-18-CE14-0039-01). LB is supported by a fellowship from the Fondation pour la Recherche Médicale (FRM).