What we investigate

Our research focuses on the understanding of mechanisms that initiate and maintain inflammation in the skin. Amongst others, one of those mechanisms involves dermal infiltration by plasmacytoid dendritic cells and their activation to produce type I interferons.

KEYWORDS
plasmacytoid dendritic cells (pDCs), psoriasis, skin inflammation, tumor microenvironment, venereology

Comparison of paradoxical psoriasis <em>(left)</em> and classical psoriasis <em>(right)</em> in CD8 stainings. Dashed lines indicate the border between the dermis and epidermis. Arrows indicate intraepidermal CD8<sup>+</sup> T cells in paradoxical psoriasis. Scale bars represent 50 μm.
Comparison of paradoxical psoriasis (left) and classical psoriasis (right) in CD8 stainings. Dashed lines indicate the border between the dermis and epidermis. Arrows indicate intraepidermal CD8+ T cells in paradoxical psoriasis. Scale bars represent 50 μm.
Our research in more detail

Understanding cellular and molecular pathways involved in inflammation of the skin is the focus of our research. For dermal infiltration by pDCs, as mentioned above, we identified a new inflammatory pathway. We also found that this pathway is over-activated in psoriasis and lupus, where it drives chronic inflammation and disease initiation. This pathway is activated in injured skin, but it is self-limited, providing a well-controlled initial inflammatory stimulus that promotes the wound healing response.

More recently, we found that this inflammatory pathway is also at the heart of a side effect of anti-TNF treatment, called paradoxical psoriasis. In contrast to psoriasis, paradoxical psoriasis is characterized by an exaggerated activation of skin pDCs that does not lead to T cell autoimmunity. The delicate balance between TNF and type I IFN signalling can be disturbed by anti-TNF treatment, leading to paradoxical psoriasis as a side-effect of the treatment. These findings provides a basis for the design of new strategies targeting pDCs and type I IFN for the treatment and prevention of paradoxical psoriasis.

With this and other research projects, we contribute to SKINTEGRITY.CH with the aim to improve the mechanistic understanding of skin inflammation as well as its treatment in the clinic.

 
Prof. Michel Gilliet


Prof. Michel Gilliet
University of Lausanne & Lausanne University Hospital (CHUV)
Service de dermatologie et véneréologie
Avenue de Beaumont 29
1011 Lausanne

Email   Website

Selected publications

SKINTEGRITY.CH Principal Investigators are in bold:

  • Conrad C*, Di Domizio J, Mylonas A, Belkhodja C, Demaria O, Navarini AA, Lapointe AK, French LE, Vernez M and Gilliet M* (2018). TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nat Commun, 9(1), 25. *corresponding authors
  • Gestermann N#, Di Domizio J#, Lande R, Demaria O, Frasca L, Feldmeyer L, Di Lucca J and Gilliet M* (2018). Netting neutrophils activate autoreactive B cells in Lupus. J Immunol, 200, 3364. #equal contributors *corresponding author
  • Feldmeyer L, Mylonas A, Demaria O, Mennella A, Yawalkar N, Laffitte E, Hohl D, Gilliet M and Conrad C (2017). Interleukin 23-helper T cell 17 axis as a treatment target for Pityriasis Rubra Pilaris. Dermatol, 153(4), 304.