2023 Fiscal Year Research-status Report
Subclass analysis of IL-17A and osteopontin-producing T cells involved in the development of diabetic retinopathy
| Project/Area Number |
23K09036
|
|---|
| Research Institution | National Defense Medical College |
|---|
Principal Investigator |
竹内 大 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 教授 (40260939)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
佐藤 智人 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 講師 (00724246)
伊藤 正孝 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 再生発生学, 准教授 (30534896)
播本 幸三 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 助教 (80626804)
西尾 佳明 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 助教 (80727347)
|
|---|
| Project Period (FY) |
2023-04-01 – 2026-03-31
|
| Keywords | diabetes mellitus / 実験的自己免疫性ぶどう膜網膜炎 / Th17 cells / reguratory T cells / T-cell mediated immunity / AP-1 signaling pathway |
|---|
| Outline of Annual Research Achievements |
PURPOSE. Inflammation is involved in the pathogenesis of diabetes, however the impact of diabetes on organ-specific autoimmune diseases remains unexplored. Experimental autoimmune uveoretinitis (EAU) is a widely accepted animal model of human endogenous uveitis. In this study, we investigated the effects of diabetic conditions on the development of EAU using a mouse diabetes model. METHODS. EAU was induced in wild-type C57BL/6 (WT) mice and Ins2Akita (Akita) mice with spontaneous diabetes by immunization with IRBP peptide. Clinical and histopathological examinations, and analysis of T cell activation state were conducted. In addition, alternations in the composition of immune cell types and gene expression profiles of relevant immune functions were identified using single-cell RNA sequencing. RESULTS. The development of EAU was significantly attenuated in immunized Akita (Akita-EAU) mice compared with immunized WT (WT-EAU) mice, although T cells were fully activated in Akita-EAU mice, and the differentiation into Th17 cells and regulatory T (Treg) cells was promoted. However, Th1 cell differentiation was inhibited in Akita-EAU mice, and single-cell analysis indicated that gene expression associated AP-1 signaling pathway (JUN, FOS, and FOSB) was downregulated not only in Th1 cells but also in Th17, and Treg cells in Akita-EAU mice at the onset of EAU. CONCLUSIONS. In diabetic mice, EAU was significantly attenuated. This was related to selective inhibition of Th1 cell differentiation and downregulated AP-1 signaling pathway in both Th1 and Th17 cells.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
上記内容の論文を投稿し、major revisionを受け、現在再投稿中である．Akita-EAUマウスで上昇がみられたA100A8/A9が糖尿病慢性炎症に関与すると考え、今年度はそのKnock out miceで検討を行う予定である．
|
| Strategy for Future Research Activity |
．Akita-EAUマウスで上昇がみられたA100A8/A9が糖尿病慢性炎症に関与すると考え、今年度はそのKnock out miceで検討を行う予定である．
|
-
-
-
[Journal Article] Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST2023
Author(s)
Takaaki Sugisawa, Hiroto Ishikawa, Kazutaka Uchida, Yoshio Takesue, Junya Mori, Takamasa Kinoshita, Shohei Morikawa, Fumiki Okamoto, Tomoko Sawada, Masahito Ohji, Takayuki Kanda, Masaru Takeuchi, at al.
-
Journal Title
Ocul Immunol Inflamm
Volume: 31(7)
Pages: 1505-1512
DOI
Peer Reviewed
-
-
-
-
-
[Journal Article] Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan2023
Author(s)
Yoneda K, Takeuchi M, Yasukawa T, Terasaki H, Yamamoto Y, Jujo T, Wakuta M, Matsubara H, Mitamura Y, Kato A, Kondo M, Kimura K, Takagi H, Gomi F, Sakamoto T; Japanese Clinical Retinal Study (J-CREST) Group.
-
Journal Title
Ophthalmol Retina
Volume: 7(10)
Pages: 869-878
DOI
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
