IL-13 is a newly-discovered cytokine that shares several functional properties with il-4. We have observed recently that normal human keratinocytes (KC) produce IL-13 constitutively. Because Atopic Dermatitis (AD) is frequently associated with several of the immunological ~abnormalities~ that are inducible with IL-13, we hypothesize that KC-derived IL-13 plays a pathogenic role in its development and/or maintenance.
Our specific aims are: 1) To identify stimuli that modulate IL-13 production by normal human KC; 2) To characterize the production of IL-13 by KC in cutaneous lesions of AD; and 3) To study influences of IL-13 on the function of human Langerhans cells.
Under Aim 1, we will determine whether IL-13 production by KC (assessed by ELISA, RT-PCR, and Northern blotting) is regulated by cytokines, bacterial products, chemical mediators, corticosteroids, and UV radiation.
Under Aim 2, we will study IL-13 production by KC in lesional and non-lesional skin of AD patients.
Under Aim 3, we will examine the effect of IL-13 on several functional properties of Langerhans cells, including surface phenotype, IgE- capturing capacity, antigen presenting capacity, and cytokine secretion. The knowledge derived from this study will provide new insight into the pathogenesis of AD and, we anticipate that this may lead to the development of new therapeutic strategies (e.g. by blocking of IL-13- dependent intercellular communication in skin).
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