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Michel Gilliet
The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA
Michel Gilliet received his MD from the University of Zurich Medical School (Switzerland) in 1995. He then went on to do his clinical training in dermatology at the University of Zurich. During his clinical residency he spent 2 years as a postdoctoral research fellow at the DNAX Research Institute, Palo Alto (USA), in the lab of Yong-Jun Liu, where he studied the role of plasmacytoid dendritic cells in CD8 T cell-mediated immunological tolerance. After completing his residency in dermatology in Zurich, he returned to the US as a faculty member of The University of Texas M. D. Anderson Cancer Center. Since 2005 Michel Gilliet is Associate Professor in Dermatology, Immunology and Melanoma Medical Oncology. He is working as a certified dermatologist and leads an active research group.
Michel Gilliet’s research focuses on investigating the role of dendritic cells in the pathogenesis of auto-inflammatory skin diseases. His group was recently able to provide new insights into how dendritic cells initiate and drive auto-inflammation in psoriasis. Based on the finding that plasmacytoid dendritic cells are found in the skin of psoriatic patients, he was able to show that interferon-alpha production by plasmacytoid dendritic cells represents a critical step in triggering disease formation. The recent ground-braking discovery by his group that plasmacytoid dendritic cells are able to recognize self-DNA and -RNA when complexed with antimicrobial peptides provides us with a novel mechanism of how dendritic cells could drive auto-inflammation in psoriasis.
ANTIMICROBIAL PEPTIDES AND THE BREAK OF INNATE TOLERANCE TO SELF-NUCLEIC ACIDS
Plasmacytoid dendritic cells (pDC) sense viral nucleic acids via intracellular Toll-like receptors (TLR)-7 and -9 and initiate protective immunity against viruses through the production of type I interferons (IFN). Normally, host-derived (self) nucleic acids released by dying cells fail to access intracellular TLR-7 and -9 compartments. However, self-nucleic acids gain access to intracellular TLR compartments to trigger high levels of IFNs in pDC when complexed with endogenous antimicrobial peptides. These peptides are typically expressed transiently in skin wounds, where they induce a short-lived activation of pDC that appears to be critical for immune activation and the initiation of the wound healing response. By contrast, antimicrobial peptides are continuously overexpressed in skin lesions of psoriasis, where they trigger chronic pDC activation and IFN-driven autoimmunity.
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