The goal of the laboratory is to understand the mechanisms that underlie 45tissue homeostasis and its breakdown during disease development. As a most recent focus, we have been studying the mechanisms by which sensory nerves are activated to induce pathogenic pruritus in inflammatory skin condi-tions such as atopic dermatitis. In 2023, we have published our findings regard-ing the roles for the sensory neuronal IL-31 receptor and STAT3 in inflamma-tory itch using the mouse model of atopic dermatitis (Figure). This study has also revealed that subcutaneously injected IL-31 activates STAT3, not only in the IL-31 receptor-expressing neurons but also in other itch-transmitting sen-sory neurons. This finding may explain why IL-31 can enhance itch induced by various pruritogens such as leukotriene C4 and chloroquine, which are thought to activate different subsets of sensory neurons.We have also published the results of our collaborative work with expert researchers in the field of drug delivery. The work has revealed that an mRNA vaccine equipped with an ionizable lipid material with a vitamin E scaffold transfects type 2 conventional dendritic cell subset (cDC2), induces the presen-tation of mRNA vaccine antigens on MHC class I of the cDC2 cells, and elicits efficient CD8+ T cell responses.Figure: The role for STAT3 in the IL-31 receptor-expressing sensory neuronSensory neuronal STAT3 is important for expression of the IL-31 receptor composed of the IL-31RA and OSMR subunits. STAT3 is also involved in the signaling pathway downstream of the IL-31 receptor and other cytokine receptors to induce itch. The candidate genes upregu-lated by activated STAT3 in sensory neurons include Nppb encoding a peptide hormone BNP.Recent Major PublicationsUsui K, Nakashima C, Takahashi S, Okada T, Ishida Y, Na-kajima S, Kitoh A, Nomura T, Dainichi T, Honda T, Katsu-moto R, Konishi N, Matsushita M, Otsuka A, Kabashima K. TRPV1-positive sensory nerves and neuropeptides are involved in epidermal barrier repair after tape strip-ping in mice. J Allergy Clin Immunol 153, 868-873.e4 (2023)Takahashi S, Ochiai S, Jin J, Takahashi N, Toshima S, Ishigame H, Kabashima K, Kubo M, Nakayama M, Shiro-guchi K, Okada T. Sensory neuronal STAT3 is critical for IL-31 receptor expression and inflammatory itch. Cell Rep 42, 113433 (2023)Oyama R#, Ishigame H#, Tanaka H, Tateshita N, Itazawa M, Imai R, Nishiumi N, Kishikawa JI, Kato T, Anindita J, Nishikawa Y, Maeki M, Tokeshi M, Tange K, Nakai Y, Sakurai Y, Okada T*, Akita H*. (co-first authors#, co-corresponding authors*) An Ionizable Lipid Material with a Vitamin E Scaffold as an mRNA Vaccine Platform for Efficient Cytotoxic T Cell Responses. ACS Nano 17, 18758-18774 (2023)Invited presentationsOkada T. “Characterization of sensory nerves tranmitting itch during skin barrier impairment and inflammation” The 96th Annual Meeting of the Japanese Biochemical Society (Fukuoka, Japan) November 2023Okada T. “The role for sensory neuronal IL-31 receptor and STAT3 in inflammatory itch” JSICR/MMCB 2023 Joint Symposium (Wakayama, Japan) May 2023Okada T. “Characterization of sensory nerves transmit-ting itch during skin barrier impairment and inflam-mation” The 1st International Societies for Investigative Dermatology Meeting, Symposium for Platinum Sponsor (Tokyo, Japan) May 2023Laboratory for Tissue DynamicsTeam Leader: Takaharu Okada
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