Jin H, Oyoshi MK, Le Y, et al. J Clin Invest. 2009;119(1):47–60
PURPOSE OF THE STUDY. To examine the role of interleukin 21 (IL-21) in the pathogenesis of atopic dermatitis (AD).
STUDY POPULATION. Nine subjects with acute AD lesions and 5 healthy control subjects.
METHODS. Samples were obtained for skin biopsy and immunohistochemical analysis of IL-21 and IL-21 receptor (IL-21R) levels. A murine model for epicutaneous sensitization and dermatitis induced by repetitive application of antigen (ovalbumin) or hapten (oxazolone) after mechanical injury (tape stripping) was then used to examine the role of the IL-21 pathway in dendritic cell activation and migration and T cell stimulation.
RESULTS. The expression of IL-21 and IL-21R was elevated in acute AD lesions, compared with the normal skin of healthy control subjects. IL-21 was most strongly expressed in mononuclear cells in the dermis, whereas IL-21R was most strongly expressed by keratinocytes. Two wild-type mouse strains develop allergic epicutaneous sensitization after antigen or hapten application to skin that has been damaged by tape stripping. Il-21r-knockout mice, which lack expression of the receptor, are deficient in both the development of local inflammation and the associated T-helper 2-skewed systemic immune response. Il-21r-deficient dendritic cell populations are normal in their capacity to induce naive T cell activation; however, they are abnormal in their ability to upregulate chemokine receptor 7 and to migrate appropriately to draining lymph nodes after minor skin trauma.
CONCLUSIONS. IL-21 and IL-21R expression is elevated in acute AD lesions, and IL-21R is required in a model of epicutaneous allergic sensitization that resembles human AD.
REVIEWER COMMENTS. The etiology of AD in unknown, although recent studies underscored a role for skin barrier defects that might enhance allergic sensitization. The discovery in this report of the importance of IL-21 for epicutaneous sensitization, along with the observed elevation of IL-21/IL-21R in human AD lesions, suggests that this pathway may be a key player in the vicious cycle of barrier defect, sensitization, inflammation, and worsening barrier defect. IL-21 is also known in other models to induce T-helper 17 cells and to suppress immunoglobulin E, neither of which was reported in this study and which may not accord so well with our current understanding of AD. Nevertheless, this early report may be a first step toward identifying a new target for intervention and treatment.
- Copyright © 2009 by the American Academy of Pediatrics