IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema

Sara M Lind1, Carlotta Kuylenstierna, Markus Moll

  • 1Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Insights

Interleukin-18 (IL-18) activates invariant natural killer T (iNKT) cells in atopic eczema (AE). Chronic IL-18 exposure suppresses CD4(+) iNKT cells, correlating with AE severity and IgE levels.

Area of Science:

  • Immunology
  • Dermatology
  • Microbiology

Background:

  • Atopic eczema (AE) is a chronic inflammatory skin condition.
  • The yeast Malassezia can trigger AE flares.
  • Interleukin-18 (IL-18), an innate cytokine elevated in AE patients, is produced by dendritic cells activated by Malassezia.

Purpose of the Study:

  • To investigate the role of IL-18 in the human invariant NKT (iNKT) cell compartment in AE.
  • To understand how IL-18 affects iNKT cell responses in the context of AE pathogenesis.

Main Methods:

  • Investigated the effect of IL-18 on human iNKT cells in vitro.
  • Analyzed iNKT cell populations (CD4+ vs. CD4-) in peripheral blood of AE patients.
  • Measured plasma levels of IL-18, total IgE, and correlated these with disease severity.

Main Results:

  • IL-18 potently activates human iNKT cells, inducing a pro-inflammatory CD1d-dependent response.
  • Chronic IL-18 exposure inhibits iNKT cells, specifically suppressing CD4+ iNKT cells.
  • AE patients exhibit reduced CD4+ iNKT cell proportions, elevated IL-18 plasma levels, and a correlation between IL-18, IgE, and disease severity.

Conclusions:

  • IL-18 plays a significant role in the pathogenesis of human atopic eczema.
  • Dysregulation of CD1d-restricted iNKT cells by IL-18 contributes to AE development.
  • Targeting IL-18 or modulating iNKT cell responses could be potential therapeutic strategies for AE.