| First Author | Lind SM | Year | 2009 |
| Journal | Eur J Immunol | Volume | 39 |
| Issue | 8 | Pages | 2293-301 |
| PubMed ID | 19637196 | Mgi Jnum | J:151774 |
| Mgi Id | MGI:4355261 | Doi | 10.1002/eji.200839195 |
| Citation | Lind SM, et al. (2009) IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema. Eur J Immunol 39(8):2293-301 |
| abstractText | Atopic eczema (AE) is a chronic relapsing inflammatory skin disease where the commensal yeast Malassezia can act as a microbial trigger factor. Malassezia activates human DC to produce IL-18, an innate cytokine that is elevated in serum of AE patients; however, the precise role of IL-18 in human AE etiology is unknown. Herein, we investigated the effect of IL-18 on the human invariant NKT (iNKT) cell compartment in AE. We found that IL-18 was a potent activator of human iNKT-cells and promoted a pro-inflammatory CD1d-dependent response, even in the absence of exogenous ligands. Chronic activation via IL-18 on the other hand was inhibitory and skewed the iNKT-cell pool by selectively suppressing CD4(+) iNKT-cells. This was mimicked in AE patients where the proportion of CD4(+) iNKT-cells was reduced in peripheral blood and coincided with elevated plasma levels of IL-18. Furthermore, a reduced CD4(+) iNKT-cell pool was associated with elevated IgE levels in plasma, and the plasma levels of IL-18 correlated with both total IgE and disease severity in the AE patients. Based on these findings, we propose that IL-18-mediated activation and subsequent dysregulation of the CD1d-restricted iNKT-cells plays a role in the pathogenesis of human AE. |
