Joint SFB 1054 & SFB 1335 Seminar - Emma Guttman-Yassky

Title: Atopic Dermatitis – From Pathogenic Advances to Novel Therapeutic Developments

 We are experiencing a paradigm shift in the pathogenesis of AD, with growing evidence for the primary role of polar immune activation in triggering abnormal keratinocyte responses. In the last decade, Th2 and Th22 cytokines were reported to modulate the epidermal barrier, including suppression of keratinocyte differentiation and lipid production, hyperplasia, and production of antimicrobial peptides (AMPs). Patients with AD have also been shown to have high levels of circulating cytokines and activation of T-cell lymphocytes in blood. The systemic nature of AD is also reflected in the abnormalities seen in the “visibly normal” or non-lesional skin of AD patients that has been shown to reflect many of the barrier and immune abnormalities that are characteristic of lesional AD skin, unlike psoriasis, in which the non-lesional skin closely mirrors the normal skin phenotype. The systemic immune activation and significant pathology in NL skin of severe AD patients might explain the frequent need for systemic immune-suppressants and the inadequacy of treating only LS skin with topical agents in this patient population. Recent studies suggest that different AD phenotypes are associated with distinct patterns of activation (or suppression) of polar immune axes and corresponding tissue responses, possibly suggesting that different therapeutics might be required to effectively treat various AD subsets (i.e pediatric vs adult AD, European AD vs Asian AD or African American etc). Selection of immune targeted therapeutics for patients with different disease severities or recognized AD phenotypes should not be done by serendipity but should be guided by defining the extent of activation of polar immune circuits in skin and blood. For example, we have recently showed using an IL-22 antagonist that in patients with high IL-22 expression at baseline an IL-22 antagonist (ILV-094) shows good efficacy, whereas in patients with low expression, there is no benefit in this treatment. Multiple axes are now targeted in AD, and future studies with mechanistic correlates will be able to direct us towards a personalized medicine approach in AD.

Emma Guttman-Yassky - Website

Venue:

BioMedical Center (BMC), Room N 02.017,
Großhaderner Str. 9, Planegg-Martinsried

Host: Christina Zielinski (B10)

If you wish to talk to the speaker, please contact Katharina.Frank@med.uni-muenchen.de