Elucidation of the role of regulatory T cells in autoimmune ocular inflammatory diseases

• Project/Area Number: 25462757
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kochi University
• Principal Investigator: FUKUSHIMA Atsuki 高知大学, 教育研究部医療学系臨床医学部門, 教授 (40281737)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 胸腺 / 自己免疫病 / 制御性T細胞 / aire遺伝子 / ヌードマウス / 自己抗体 / 網膜 / 涙腺 / 移植

Outline of Final Research Achievements

When F344 embryonic rat thymus was transplanted beneath the renal capsule of BALB/c nude mice, the mice acquired the immunity of mouse origin. Autoimmune regulator (aire) gene was expressed in the rat thymic medullary epithelial cells, and enough regulatory T cells (Treg) presented in the periphery, however severe organ-localized autoimmune diseases developed. When Treg population of the normal mouse was injected before the symptoms of autoimmune diseases developed in TG nude mice, the onset of the diseases has been prevented.

Research Products

• [Journal Article] One-year clinical evaluation of 0.4% ripasudil (K-115) in patients with open-angle glaucoma and ocular hypertension. (2016)
  • Author(s): Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Fukushima A, Suganami H, Araie M; K-115 Clinical Study Group.
  • Journal Title: Acta Ophthalmologica Volume: 94 Issue: 1 Pages: 26-34
  • DOI: 10.1111/aos.12829
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of NF90-NF45 represses myogenic microRNA biogenesis, developing skeletal muscle atrophy and centronuclear muscle fibers (2015)
  • Author(s): Hiroshi Todaka, Takuma Higuchi, Ken-ichi Yagyu, Yasunori Sugiyama, Fumika Yamaguchi, Keiko Morisawa, Masafumi Ono, Atsuki Fukushima, Masayuki Tsuda, Taketoshi Taniguchi, Shuji Sakamoto
  • Journal Title: Molecular and Cellular Biology Volume: 35 Issue: 13 Pages: 2295-2308
  • DOI: 10.1128/mcb.01297-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1β in human corneal fibroblasts. (2015)
  • Author(s): Inokawa S, Watanabe T, Keino H, Sato Y, Hirakata A, Okada AA, Fukuda K, Fukushima A, Umezawa K.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. Volume: 253 Issue: 4 Pages: 557-563
  • DOI: 10.1007/s00417-014-2879-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prevention of allergic conjunctivitis in mice by a rice-based edible vaccine containing modified Japanese cedar pollen allergens. (2015)
  • Author(s): Fukuda K, Ishida W, Harada Y, Wakasa Y, Takagi H, Takaiwa F, Fukushima A.
  • Journal Title: Br J Ophthalmol. Volume: - Issue: 5 Pages: 705-709
  • DOI: 10.1136/bjophthalmol-2014-305842
  • Peer Reviewed / Open Access
• [Journal Article] The roles of epithelial cell-derived type 2 initiating cytokines in experimental allergic conjunctivitis. (2015)
  • Author(s): Asada Y, Nakae S, Ishida W, Hori K, Sugita J et al.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 56 Issue: 9 Pages: 5194-5202
  • DOI: 10.1167/iovs.15-16563
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 高知大学附属病院眼科における視神経炎の治療の検討. (2015)
  • Author(s): 三浦 悠作, 笠井 真央, 福田 憲, 高橋 利幸, 福島 敦樹
  • Journal Title: 臨床眼科 Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] 眼科アレルギー診療 編集企画にあたって・・・. (2015)
  • Author(s): 福島 敦樹
  • Journal Title: OCULISTA Volume: 24 Pages: 1-1
  • Peer Reviewed / Open Access
• [Journal Article] アレルギー性結膜疾患の難治症例 総論 (2015)
  • Author(s): 福島 敦樹
  • Journal Title: NANO OPHTHALMOLOGY Volume: 47 Pages: 2-2
  • Peer Reviewed
• [Journal Article] 日本眼科アレルギー研究会 Special Interest Group Meeting (SIG)報告. (2015)
  • Author(s): 福島 敦樹
  • Journal Title: 臨床眼科 Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] 特集／アレルギー性結膜疾患 アップデート Ⅱ．結膜充血の定量的評価 (2015)
  • Author(s): 福島 敦樹
  • Journal Title: アレルギー・臨床免疫 Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] アレルギー性結膜疾患－アトピーに伴うもの以外－ 別冊ＢＩＯ Ｃｌｉｎｉｃａ 慢性炎症と疾患 (2015)
  • Author(s): 福島 敦樹
  • Journal Title: 眼疾患と炎症 Volume: 4(3) Pages: 32-37
  • Peer Reviewed / Open Access
• [Journal Article] ぶどう膜炎の病型別分類：疫学調査から学ぶこと (2015)
  • Author(s): 福島 敦樹
  • Journal Title: 日本眼科学会雑誌 Volume: 119(10) Pages: 667-669
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of very late antigen-4 and leukocyte function-associated antigen-1 in experimental autoimmune uveoretinitis. (2014)
  • Author(s): Ishida W, Harada Y, Fukuda K, Taguchi O, Yagita H, Fukushima A.
  • Journal Title: Clin Immunol Volume: 153 Pages: 136-144
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition by rebamipide of cytokine- or lipopolysaccharide-induced chemokine synthesis in human corneal fibroblasts. (2014)
  • Author(s): Fukuda K, Ishida W, Tanaka H, Harada Y, Fukushima A.
  • Journal Title: Br J Ophthalmol Volume: 98 Issue: 12 Pages: 1751-1755
  • DOI: 10.1136/bjophthalmol-2014-305425
  • Peer Reviewed / Open Access
• [Journal Article] Oral immunotherapy for allergic conjunctivitis. (2014)
  • Author(s): Ishida W, Fukuda K, Harada Y, Yagita H, Fukushima A.
  • Journal Title: Cornea. Volume: 33 suppl11
  • Peer Reviewed / Open Access
• [Journal Article] ぶどう膜炎: アレルギーが関与する眼疾患. アレルギーと眼疾患. (2014)
  • Author(s): 福島敦樹
  • Journal Title: アレルギーの臨床 Volume: 34(11) Pages: 1138-1138
  • Peer Reviewed
• [Journal Article] Oral administration of Ag suppresses Ag-induced allergic conjunctivitis in mice: critical timing and dose of Ag. (2013)
  • Author(s): Ishida W, Fukuda K, Harada Y, Sumi T, Taguchi O, Tsuda M, Yagita H, Fukushima A.
  • Journal Title: Br J Ophthalmol Volume: 97(4) Issue: 4 Pages: 492-497
  • DOI: 10.1136/bjophthalmol-2012-302639
  • Peer Reviewed
• [Journal Article] Behavior of bone marrow-derived cells following in vivo transplantation: differentiation into stromal cells with roles in organ maintenance. (2013)
  • Author(s): Taguchi O, Tsujimura K, Kontani K, Harada Y, Nomura S, Ikeda H, Morita A, Sugiura H, Hayashi N, Yatabe Y, Seto M, Tatematsu M, Takahashi T, Fukushima A.
  • Journal Title: Am J Pathol Volume: 182(4) Issue: 4 Pages: 1255-1262
  • DOI: 10.1016/j.ajpath.2012.12.034
  • Peer Reviewed
• [Journal Article] Rebamipide increases barrier function and attenuates TNF-α-induced barrier disruption and cytokine expression in human corneal epithelial cells. (2013)
  • Author(s): Tanaka H, Fukuda K, Ishida W, Harada Y, Sumi T, Fukushima A.
  • Journal Title: Br J Ophthalmol Volume: 97(7) Issue: 7 Pages: 912-916
  • DOI: 10.1136/bjophthalmol-2012-302868
  • Peer Reviewed
• [Journal Article] Alarmins from corneal epithelial cells up-regulate CCL11 and VCAM-1 in corneal fibroblasts. (2013)
  • Author(s): Fukuda K, Ishida W, Tanaka H, Harada Y, Matsuda A, Ebihara N, Fukushima A.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54(8) Issue: 8 Pages: 5817-5823
  • DOI: 10.1167/iovs.13-11969
  • Peer Reviewed
• [Journal Article] Identification of keratocyte-like cells differentiated from circulating bone marrow-derived cells in the mouse cornea. (2013)
  • Author(s): Harada Y, Ishida W, Fukuda K, Sumi T, Kawakita T, Taguchi O, Fukushima A.
  • Journal Title: Med Mol Morphol Volume: 46 Issue: 4 Pages: 233-238
  • DOI: 10.1007/s00795-013-0031-2
  • Peer Reviewed