Inflammatory skin disease, Interleukin 9 (IL-9), PPAR-γ, Skin-resident T-cells, T helper cells
What we investigate
Our research is focused on the role of T helper cells in inflammatory and malignant skin disease. In particular, we are interested in skin-resident TH2 cells and the function of interleukin-9-producing "TH9" cells. More recently, we have also focussed on the investigation of the transcription factor PPARγ in human "pathogenic" TH2 cells.
Our research in more detail
Skin-resident memory T (TRM) cells persist long-term in the skin to provide immune protection. However, their activation by allergens or autoantigens can cause chronic inflammatory skin disease. Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common T cell-driven diseases in which TRM cells play a key role and contribute to their chronicity. Current treatments suppress inflammation, but fail to cure patients long-term. Thus, there is a need for a better understanding of pathogenic TRM in T helper 2 cell (TH2)-driven skin disease, such as AD and ACD, as a prerequisite for the development of curative therapies.
New evidence suggests that PPARγ constitutes a link between TRM and TH2-driven skin disease, which is of major interest given the large potential of targeting PPARγ for therapeutic purposes. Interestingly, mouse models suggest that both pathogenic TH2 cells and skin TRM critically depend on PPARγ. Yet, the importance and function of PPARγ in human skin TH cells remain unknown. Our research aims to elucidate the functional importance of PPARγ for TH2 cells in human skin to develop curative rather than merely suppressive treatments for chronic inflammatory skin disease.
SKINTEGRITY.CH Principal Investigators are underlined:
- Schlapbach C, Yang C, Watanabe R, Gehad A, Guenova E, Teague J, Yawalkar N, Kupper TS and Clark RA (2014). Human TH9 cells are skin-tropic and have autocrine and paracrine pro-inflammatory capacity. Sci Transl Med 6: 219ra8.
- Micossé C, von Meyenn L, Adam C, Simillion C, Jafari SMS, Olah P, Yawalkar N, Simon D, Borradori L, Kuchen S, Homey B, Snijder B, Schmidt M, Yerly D, and Schlapbach C (2019). Human “TH9” cells are a subpopulation of PPAR-γ+ TH2 cells. Sci Immunol 4; eaat5934
- Hartwig T, Zwicky P, Schreiner B, Yawalkar N, Cheng P, Navarini A, Dummer R, Flatz L, Conrad C, Schlapbach C and Becher B (2018). Regulatory T cells restrain pathogenic T helper cells during skin inflammation. Cell Rep 25: 3564-3572.
- Jafari SMS, Gadaldi K, Feldmeyer L, Yawalkar N, Borradori L and Schlapbach C (2019). Effects of omalizumab on FcεRI and IgE expression in lesional skin of bullous pemphigoid. Front Immunol 10: 2285.