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.


CONCLUSIONS
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.


CONCLUSIONS
Understanding the potential role of iNKT cells in AD will allow us to have a more specific target for therapeutic use.
Elkhal
Abdallah
A
Division of Immunology, Children's Hospital, Boston. MA 02115, USA.
Pichavant
Muriel
M
He
Rui
R
Scott
Jordan
J
Meyer
Everett
E
Goya
Sho
S
Geha
Raif S
RS
Umetsu
Dale T
DT
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000473:pathology; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000009:adverse effects; D012867:Skin / Q000276:immunology* / Q000473:pathology
D000485:Allergens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D007378:Interleukins; D010047:Ovalbumin