Regulation of immunometabolism in the dendritic cells by intratissue commensal bacteria
| Project/Area Number |
18H02674
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 49070:Immunology-related
|
|---|
| Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition |
|---|
Principal Investigator |
Kunisawa Jun 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ワクチン・アジュバント研究センター, センター長 (80376615)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
|---|
| Keywords | 腸内細菌 / 免疫メタボリズム / 組織内共生 / 樹状細胞 / バイオインフォマティクス解析 / 共生細菌 / 腸管免疫 / マクロファージ |
|---|
| Outline of Final Research Achievements |
We examined the interaction between the intestinal lymphoid tissue resident commensal bacteria and immune cells, and clarified the symbiotic mechanism at the cellular and molecular levels. Alcaligenes, a symbiotic bacterium inside Peyer's patches (PPs), promotes the production of cytokines that promote IgA antibody production from dendritic cells (DCs), but induces little production of nitric oxide, leading to the enhanced immune responses without causing excessive inflammation. Thus, it is considered that Alcaligenes contributes to the activation of appropriate immune responses while maintaining immunological homeostasis. Furthermore, Alcaligenes may establish a sustainable symbiotic relationship within PPs through increasing mitochondrial activity and suppressing apoptotic cell death of DCs.
|
| Academic Significance and Societal Importance of the Research Achievements |
アルカリゲネスの免疫学的ユニーク性の一端は、本菌のリポ多糖（LPS）やその活性中心であるリピドAの特殊な構造と免疫学的性状によって説明できる。そこで、適度な免疫活性化作用をもつアルカリゲネスLPSやリピドAを活用したワクチンアジュバントの開発を進め、皮下や経鼻ワクチンに対して有効性と安全性のバランスに優れたアジュバント効果を発揮することを明らかにした。現在、実験用アジュバントとして販売され、また、ワクチン・製薬メーカーと共同で非臨床試験など実用化に向けた検討を進めており、本研究で得られた学術知見を基盤として、アジュバント開発を目指した応用研究へ発展しており、社会的にも意義のある研究である。
|
Report
(4 results)
Research Products
(121 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia2019
Author(s)
Takahashi Ichiro, Hosomi Koji, Nagatake Takahiro, Tobou Hirokazu, Yamamoto Daiki, Hayashi Ikue, Kurashima Yosuke, Sato Shintaro, Shibata Naoko, Goto Yoshiyuki, Maruyama Fumito, Nakagawa Ichiro, Kuwae Asaomi, Abe Akio, Kunisawa Jun, Kiyono Hiroshi
-
Journal Title
International Immunology
Volume: 32
Issue: 2
Pages: 133-141
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] 17(S),18(R)-epoxyeicosatetraenoic acid generated by cytochrome P450 BM-3 from Bachillus megaterium inhibits the development of contact hypersensitivity via G-protein-coupled receptor 40-mediated neutrophil suppression2019
Author(s)
Saika A, Nagatake T, Kishino S, Park S, Honda T, Matsumoto N, Shimojou M, Morimoto S, Tiwari P, Node E, Hirata SI, Hosomi K, Kabashima K, Ogawa J, and Kunisawa J
-
Journal Title
FASEB BioAdvances
Volume: 2
Issue: 1
Pages: 59-71
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] BLT1 Mediates Commensal Bacteria-Dependent Innate Immune Signals to Enhance Antigen-Specific Intestinal IgA Responses2019
Author(s)
Nagatake T, Hirata SI, Koga T, Kuroda E, Kobari S, Suzuki H, Hosomi K, Matsumoto N, Yanrismet Y, Shimojou M, Morimoto S, Sasaki F, Ishii KJ, Yokomizo T, Kunisawa J.
-
Journal Title
Mucosal Immunol .
Volume: 12
Issue: 5
Pages: 1082-1082
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
[Journal Article] Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity2018
Author(s)
N. Shibata, J. Kunisawa, K. Hosomi, Y. Fujimoto, K. Mizote, N. Kitayama, A. Shimoyama, H. Mimuro, S. Sato, N. 5 Kishishita, K. J. Ishii, K. Fukase, and H. Kiyono
-
Journal Title
Mucosal Immunology
Volume: －
Issue: 3
Pages: 693-702
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
