Understanding the mechanism of local immune induction from the perspective of induced skin-associated lymphoid tissue (iSALT)
Grantee: Kenji Kabashima, Professor, Kyoto University Graduate School of Medicine, Japan
Amount: DKK 4,000,000
Grant category: Research Grants in open competition
Year: 2024
Geography: Japan
Kenji Kabashima’s project explores the hypothesis that skin possesses the capacity for independently initiating acquired immune responses. More specifically, it aims to investigate the hypothesis that “skin functions as a site for induction of diverse immune responses” by leveraging the inducible skin-associated lymphoid tissue (iSALT) previously discovered by Kenja Kabashima and his team. The objectives are to establish a novel method for local immune manipulation utilizing iSALT and to elucidate the mechanisms underlying the induction of various immune responses within the local skin environment. To achieve these goals, an innovative approach is proposed: combining verification of iSALT existence in human skin, functional characterization of iSALT, application of 3D bioprinter technology, development of human skin organoids, implementation of cutting-edge skin imaging techniques, and utilization of multi-omics analyses. The expected outcomes include elucidation of molecular mechanisms governing immune regulation in local skin areas, potential applications in treating immunological and inflammatory skin diseases, and insights into managing skin malignancies.
The results of Kenji Kabashima’s research have the potential to significantly advance our understanding of skin immunology and open new avenues for therapeutic interventions in dermatological conditions.
Cytosolic genome DNA fragments as a trigger of keratinocyte proliferation in psoriasis
Grantee: Dr Koichi Suzuki, PhD, Professor, Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University
Amount: DKK 460,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Japan
Release of double-stranded (ds)DNA from keratinocytes has been linked to the initiation of psoriasis via induction of an immune response. Furthermore, vitamin D has been reported to interfere with this mechanism. Vitamin D analogues are widely used for treatment of psoriasis and have a well-known effect on keratinocyte proliferation and differentiation.
Dr Koichi Suzuki and his Japanese-Chinese team hypothesise that the release of dsDNA may more directly induce the characteristic hyper-proliferation and abnormal differentiation of keratinocytes seen in psoriasis by a TNFα-mediated inflammatory process in keratinocytes.
The team will investigate this hypothesis and the impact of vitamin D by the use of keratinocyte cultures and psoriasis skin samples from patients treated with a vitamin D analogue.
The project may further enhance our understanding of the complex molecular events underlying psoriasis and how vitamin D treatment may intervene in the pathogenic process, potentially revealing new aspects of the mode of action of vitamin D.