The development of atopic dermatitis (AD), a common chronic inflammatory skin diseases, is thought to be influenced by both environmental factors (allergens) and by genetic factors that control immunological responsiveness to the relevant allergens. Because of their remarkable ability to initiate and regulate cutaneous immune responses, epidermal Langerhans cells (LC), the principal antigen presenting cells (APC) in skin, are thought to play a pivotal role in both the induction and amplification of the inflammation in AD. Moreover, recent evidence show that LC from AD skin differ, both phenotypically and functionally, from those isolated from the skin of normal individuals. These differences may exist at the level of LC precursors as well, since LC-like DC precursor CD14+ cells of AD patients are phenotypically and functionally different from LC-like DC generated from counterpart precursors of healthy individuals. The goal of this pilot and feasibility (P&F) study is to characterize the intrinsic properties of LC precursors that govern their differentiation towards the abnormal phenotype characteristic of that seen in patients with AD. The proposed studies are related to, but nonetheless a distinct departure from the PI's previous research focus.
The specific aims are:
Aim 1. To determine whether phenotypic abnormalities exist at the level of DD14+ LC precursors in AD.
Aim 2. To determine whether genetic polymorphisms reported for AD are present in CD14+ LC precursors of AD patients.
Aim 3. To determine whether CD14+ precursors from AD patients vs. normal controls are differentially regulated by specific cytokines.
Aim 4. To examine whether drugs used for treatment of AD modulate properties of LC CD14+ precursors.
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