Monday, October 5, 2015
Atopic dermatitis in children shows an imbalance in cytokine production by their skin homing cells
While pediatric atopic dermatitis (AD) is a common disorder among children, our current understanding of its mechanisms derives largely from studies of adults with long-standing disease. Defining the similarities and differences between activated polarized T-cells in adults and in children with early-onset AD is critical for understanding initial events in disease causation. Further, a better understanding of newly diagnosed disease could help clarify the sequence of events that leads to AD development. Czarnowicki et al compare differences between T-cell memory subset activation within the skin homing and non-skin homing systemic compartments, as well as frequencies of polarized T cell subsets in blood of pediatric and adult patients with AD (J Allergy Clin Immunol 2015; 136(4):941-951). Specifically, they study children with AD, children of the same age without AD, and adults with AD of similar severity.
The authors find that TH2 activation, known to induce allergy, within skin-homing T-cells may drive AD in children, with concomitant reduced counter-regulation by TH1 T-cells involved in infection control. The TH22 “spreading” of AD common in adults with the condition is not evident in young children, and immune development, disease chronicity, or recurrent skin infections may influence it in the older population. While adults with AD demonstrate higher IL-22+ values (known to reduce skin barrier proteins) in skin homing T cells than adult control subjects or children with AD, there are no such differences between healthy children and children with AD. Acute lesions with redness and dryness tend to characterize AD in infants and young children, whereas adults with longstanding disease have marked thickening of lesions. Their data support a role for IL-22 in disease chronicity but not in disease initiation.
Studies have shown that many children outgrow their AD by 10 years of age. Czarnowicki et al suggest age-related disease resolution may reflect increased differentiation of TH1 T-cells to counter-regulate increased TH2 cell numbers which suppress TH2 production. While adults may benefit from IL-22-targeted therapies, approaches to treat AD in children may best be directed to correction of TH2/TH1 imbalance.