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Carlo Pincelli, MD, PhD
University of Modena & Reggio Emiliana
Modena, Italy
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Prof. Pincelli earned his MD and the Specialization in Dermatology from the University of Modena and Reggio Emilia. He was trained at research institutions internationally (St. John's Hospital for Diseases of the Skin in London, Department of Dermatology, the University of California in San Francisco, and School of Medicine at Boston University, Boston). For 30 years, he has held the position of Professor of Dermatology and Director of Research at the DermoLab of the University of Modena and Reggio Emilia, where he is currently a Consultant and Senior Professor.
Prof Pincelli is an Honorary Member of the European Society for Dermatological Research (ESDR), where he served as President in 2007. He received the Pro-Meritis Award from the European Dermatology Forum for his outstanding contribution to the advancement of Dermatology in Europe. He owns five international patents and founded two startups devoted to researching and developing new therapies in dermatology.
Last Updated: Apr 09, 2022
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PUBLICATION
IFN-k is a rheostat for development of psoriasiform inflammation. Gharaee-Kermani M, Estadt SN, Tsoi LC, Wolf-Fortune SJ, Liu J, Xing X, Theros J, Reed TJ, Lowe L, Gruszka D, Ward NL, Gudjonsson JE, Kahlenberg JM. J Invest Dermatol. 2022 Jan;142(1):155-165.e3. doi: 10.1016/j.jid.2021.05.029. Epub 2021 Aug 5. PMID: 34364883; PMCID: PMC8688309.
Why this article was chosen
This innovative research connects insights into immunopathogenesis with genetics and modes of action of treatments. More specifically, evidence is provided for keratinocytes-derived IFN-k as an early event relevant as a treatment target.
Commentary
“Rheostat” is a word coined in the nineteenth century to describe a device that regulates and adjusts the magnitude of electric current. Gharaee-Kermani et al. has recently used this term to define the newly identified role for interferon-k (IFN-k) in psoriatic lesions. They first demonstrated that IFN-regulated genes are increased in lesional and, to a lesser extent, in non-lesional psoriatic skin. They also showed that these genes correlate with psoriasis-associated cytokines, such as IL23 and IL17A. Notably, IFN-k is expressed in the psoriatic epidermis. To shed more light on the role of IFNs in the pathogenesis of psoriasis and to validate their hypothesis of IFN-k acting as a “rheostat” for psoriatic inflammation, Gharaee-Kermani and co-workers stimulated wild-type mice (WT), mice overexpressing IFN-k in the epidermis (Ifnk -TG), and mice lacking IFN-k (Ifnk-KO) with imiquimod (IMQ) to induce psoriasiform inflammation. Whereas Ifnk-KO mice developed only a mild inflammatory phenotype, ear thickness was significantly increased in Ifnk-TG compared to WT mice. The psoriatic phenotype amplified by IFN-k was further confirmed by the histopathologic features of psoriasis and the higher number of dendritic cells (DC), neutrophils, and macrophages in Ifnk-TG mice than in the other groups. Both IFN-regulated genes and genes associated with IL-17 response in psoriatic skin were significantly increased in mice that overexpressed IFN-k at the epidermal level. Finally, T-cells were more numerous in Ifnk-TG than in Ifnk-KO and WT mice. However, it should be noted that mice overexpressing IFN-k at baseline did not display a psoriasiform phenotype, suggesting that the cytokine alone is not sufficient to induce the disease. Because deletion of IFN-k attenuates the IMQ-induced inflammation, the authors concluded that targeting IFN-k may be an early treatment for psoriasis.
As pointed out by Garzorz-Stark and Kilian Eyerich1 in the Commentary related to the present article, in psoriatic skin, there are two immune axes involving IFNs: pDC-derived IFN-a and keratinocytes-derived IFN-k, both leading to type 1 (Th1, IL-12, and IFN-g) and type 3 (IL-23, Th17, IL-17) immune responses. This also implies an active role for keratinocytes in psoriasis.
- Garzorz-Stark N, Eyerich K. IFNs: Sentinels shaping distinct immune responses in skin. J Invest Dermatol (2022) 142: 14-15.
Categories:
IPC News, Blog
Tags: ifn-k, psoriasiform, commentary, pincelli