CD1d restricted natural killer T cells are not required for allergic skin inflammation

Background

Invariant T-cell receptor–positive natural killer (iNKT) cells have been shown to be essential for the development of allergen-induced airway hyperreactivity (AHR).

Objective

We examined the role of iNKT cells in allergic skin inflammation using a murine model of atopic dermatitis (AD) elicited by epicutaneous sensitization with ovalbumin (OVA).

Methods

Wild-type (WT) and natural killer T-cell–deficient CD1d^–/– mice were epicutaneously sensitized with OVA or normal saline and challenged with aerosolized OVA. iNKT cells in skin and bronchoalveolar lavage fluid were analyzed by fluorescence-activated cell sorting, and cytokine mRNA levels were measured by quantitative RT-PCR. AHR to methacholine was measured after OVA inhalation.

Results

Skin infiltration by eosinophils and CD4⁺ cells and expression of mRNA encoding IL-4 and IL-13 in OVA-sensitized skin were similar in WT and CD1d^–/– mice. No significant increase in iNKT cells was detectable in epicutaneously sensitized skin. In contrast, iNKT cells were found in the bronchoalveolar lavage fluid from OVA-challenged epicutaneously sensitized WT mice, but not CD1d^–/– mice. Epicutaneously sensitized CD1d^–/– mice had an impaired expression of IL-4, IL-5, and IL-13 mRNA in the lung and failed to develop AHR in response to airway challenge with OVA.

Conclusion

These results demonstrate that iNKT cells are not required for allergic skin inflammation in a murine model of AD, in contrast with airway inflammation, in which iNKT cells are essential.

Clinical implications

Understanding the potential role of iNKT cells in AD will allow us to have a more specific target for therapeutic use.

Key words: Atopic dermatitis, allergic skin inflammation, NKT cells, T_H2 cytokines, eosinophils

Abbreviations used: AD, Atopic dermatitis, α-GalCer, α-Galactosylceramide, AHR, Airway hyperreactivity, BAL, Bronchoalveolar lavage, FACS, Fluorescence-activated cell sorting, NK, Natural killer, NKT, Natural killer T, OVA, Ovalbumin, TCR, T-cell receptor, WT, Wild-type