Abstracts (complete list) - Wissenschaft Online

Susanne Stutte, Sabine Brauer, Irmgard Förster
FUNCTIONAL ROLE OF CCL17 IN ALLERGIC IMMUNE
REACTIONS OF THE SKIN
Professional antigen presenting cells of the skin, namely Langerhans cells (LC) and
dermal dendritic cells (DC), are continuously exposed to environmental stimuli and are
crucial for the induction of different skin immune reactions via presentation of the
antigen in draining lymph nodes (LN) and secretion of cytokines and chemokines. The
chemokine CCL17, which binds to the receptor CCR4, mediates the attraction of
activated/memory T cells to dendritic cells (DC). We generated CCL17/EGFP knockin
mice that express the enhanced green fluorescent protein (EGFP) under the control of
the endogenous ccl17 promoter. These mice can be used as heterozygous reporter mice
with normal CCL17 production or as homozygous CCL17 knockout mice which also
express the EGFP reporter. We demonstrated that the EGFP+ cells represent almost
exclusively CD11c+ DC, including activated LC and dermal DC. Functionally, the
deficiency of CCL17 leads to reduced contact hypersensitivity responses to the haptens
DNFB and FITC. Presently, we analyze the role of CCL17 expressing DC in allergic
reactions of the skin using a mouse model for atopic dermatitis (AD). Since CCL17 is
consistently upregulated in the skin of AD patients, thus chemokine may play an
important function in the pathogenesis of AD. First results indicate an essential role for
CCL17 secreting DC in the induction of the humoral immune response during chronic
skin sensitization, as CCL17 deficient mice show a decreased antigen specific IgE, IgG1
and IgG2a production. Surprisingly, in the absence of CCL17 dermal DC and LC exhibit
a reduced migratory behaviour to the skin draining LN. In addition, a lower number of
IL-4 and IL-5 secreting CD4+ T cells could be detected in skin draining LN of CCL17
knockout mice. Thus, CCL17 appears to be critically involved in the immunopathology of
atopic dermatitis.