ΔNp63 regulates IL-33 and IL-31 signaling in atopic dermatitis.

Atopic dermatitis (AD) is the most common inflammatory skin disease with no well-delineated cause or effective cure. Here we show that the p53 family member p63, specifically the ΔNp63, isoform has a key role in driving keratinocyte activation in AD. We find that overexpression of ΔNp63 in transgenic mouse epidermis results in a severe skin phenotype that shares many of the key clinical, histological and molecular features associated with human AD. This includes pruritus, epidermal hyperplasia, aberrant keratinocyte differentiation, enhanced expression of selected cytokines and chemokines and the infiltration of large numbers of inflammatory cells including type 2 T-helper cells - features that are highly representative of AD dermatopathology. We further demonstrate several of these mediators to be direct transcriptional targets of ΔNp63 in keratinocytes. Of particular significance are two p63 target genes, IL-31 and IL-33, both of which are key players in the signaling pathways implicated in AD. Importantly, we find these observations to be in good agreement with elevated levels of ΔNp63 in skin lesions of human patients with AD. Our studies reveal an important role for ΔNp63 in the pathogenesis of AD and offer new insights into its etiology and possible therapeutic targets.

Performance of children with normal and impaired oral language production on a set of auditory comprehension tests.

The purpose of this study was to investigate the comprehension abilities of children with impaired expressive language and to obtain information on the interrelationships among tests of comprehension. Forty preschool children, 20 with normal language and 20 with impaired expressive language, were given a set of auditory comprehension tests. As a group, the language-impaired children demonstrated deficits in comprehension when compared to the normal-language children. However, both groups scored near the ceiling on several tests, and on most tests that did differentiate the two groups, the mean scores of both groups when applied to performances of middle-class white children. An analysis of responses to selected groupings of analogous items revealed that a preschool child's correct response to a linguistic stimulus in one instance provides no assurance that the child will respond similarly to the stimulus in another linguistic environment with different task demands and different foil alternatives. In addition, the large majority of correlations among the test were nonsignificant, indicating that it is not clinically appropriate to regard these measures of language comprehension as equivalent.