PMID- 33777049 OWN - NLM STAT- MEDLINE DCOM- 20210927 LR - 20210927 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Inotodiol From Inonotus obliquus Chaga Mushroom Induces Atypical Maturation in Dendritic Cells. PG - 650841 LID - 10.3389/fimmu.2021.650841 [doi] LID - 650841 AB - Dendritic cells (DCs) have the ability to stimulate naive T cells that coordinate subsequent adaptive response toward an inflammatory response or tolerance depending on the DC differentiation level. Inotodiol, a lanostane triterpenoid found in Inonotus obliquus (wild Chaga mushroom), is a natural compound with a wide range of biological activities. In this study, we investigated whether inotodiol promotes the maturation of bone marrow-derived DCs (BMDCs) and inotodiol-treated BMDCs induce T cell activation. Inotodiol increased the expression of surface maturation markers, including MHC-I, MHC-II, CD86, and CD40, on BMDCs without affecting the production of various cytokines, including TNF-alpha and IL-12p40 in these cells. T cells primed with inotodiol-treated BMDCs proliferated and produced IL-2, without producing other cytokines, including IL-12p40 and IFN-gamma. Injection of inotodiol into mice induced maturation of splenic DCs and IL-2 production, and the administration of inotodiol and inotodiol-treated BMDCs induced the proliferation of adoptively transferred CD8(+) T cells in vivo. The phosphatidylinositol-3-kinase inhibitor wortmannin abrogated the upregulation of Akt phosphorylation and CD86 and MHC-II expression induced by inotodiol. However, inotodiol failed to induce phosphorylation of the IkappaB kinase and degradation of IkappaB-alpha, and increased expression of CD86 induced by inotodiol was not blocked by an IkappaB kinase inhibitor. These results suggest that inotodiol induces a characteristic type of maturation in DCs through phosphatidylinositol-3-kinase activation independent of NF-kappaB, and inotodiol-treated DCs enhance T cell proliferation and IL-2 secretion. CI - Copyright (c) 2021 Maza, Lee, Kim, Sun, Sung, Ponomarenko, Stonik, Ryu and Kwak. FAU - Maza, Perry Ayn Mayson A AU - Maza PAMA AD - Department of Pharmacology, School of Medicine, Ajou University, Suwon, South Korea. AD - Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, South Korea. FAU - Lee, Ji-Hyun AU - Lee JH AD - Department of Pharmacology, School of Medicine, Ajou University, Suwon, South Korea. AD - Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, South Korea. FAU - Kim, Yong-Su AU - Kim YS AD - Department of Pharmacology, School of Medicine, Ajou University, Suwon, South Korea. AD - Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, South Korea. FAU - Sun, Gyu-Min AU - Sun GM AD - Department of Pharmacology, School of Medicine, Ajou University, Suwon, South Korea. AD - Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, South Korea. FAU - Sung, Youn-Joo AU - Sung YJ AD - Department of Pharmacology, School of Medicine, Ajou University, Suwon, South Korea. AD - Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, South Korea. FAU - Ponomarenko, Ludmila P AU - Ponomarenko LP AD - G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia. FAU - Stonik, Valentine A AU - Stonik VA AD - G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia. FAU - Ryu, Minsook AU - Ryu M AD - Department of Allergy, School of Medicine, Ajou University, Suwon, South Korea. FAU - Kwak, Jong-Young AU - Kwak JY AD - Department of Pharmacology, School of Medicine, Ajou University, Suwon, South Korea. AD - Immune Network Pioneer Research Center, Ajou University, Suwon, South Korea. AD - 3D Immune System Imaging Core Center, Ajou University, Suwon, South Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210312 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Cytokines) RN - 0 (inotodiol) RN - 1J05Z83K3M (Lanosterol) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - Inonotus obliquus SB - IM MH - Agaricales/*chemistry MH - Animals MH - Bone Marrow Cells/*drug effects/immunology/metabolism MH - CD8-Positive T-Lymphocytes/cytology/drug effects/immunology MH - Cell Differentiation/*drug effects/immunology MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Cytokines/immunology/metabolism MH - Dendritic Cells/*drug effects/immunology/metabolism MH - Inonotus/*chemistry MH - Lanosterol/*analogs & derivatives/chemistry/pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Molecular Structure MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-akt/immunology/metabolism MH - RAW 264.7 Cells PMC - PMC7994266 OTO - NOTNLM OT - AKT1 OT - Chaga mushroom OT - IL-2 OT - atypical maturation OT - dendritic cells OT - inotodiol COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/03/30 06:00 MHDA- 2021/09/28 06:00 PMCR- 2021/01/01 CRDT- 2021/03/29 06:24 PHST- 2021/01/08 00:00 [received] PHST- 2021/02/25 00:00 [accepted] PHST- 2021/03/29 06:24 [entrez] PHST- 2021/03/30 06:00 [pubmed] PHST- 2021/09/28 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.650841 [doi] PST - epublish SO - Front Immunol. 2021 Mar 12;12:650841. doi: 10.3389/fimmu.2021.650841. eCollection 2021.