The mechanism of immunosuppressive treatment in systemic sclerosis.

• Project/Area Number: 25860955
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kumamoto University
• Principal Investigator: Makino Takamitsu 熊本大学, 大学院生命科学研究部, 講師 (20433039)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 全身性強皮症 / サイトカイン / リンパ球 / 免疫抑制剤 / mRNA

Outline of Final Research Achievements

At first, we examined the levels of proteins which extracted from skin sample of patients with systemic sclerosis (SSc) by the ELISA Array analysis. We focused on CD70 and IL-16 that were highly expressed before treatment and down-regulated after immunosuppressive therapy.Next, we performed immunohistochemistry of involved skin specimen. CD70-CD27 and IL-16 were overexpressed in the skin of SSc patients. Furthermore, soluble CD27 and IL-16 were also highly expressed in the sera of SSc patients by the sandwich ELISA.
In conclusion, CD70-CD27 signaling and IL-16 are upregulated in SSc patients, and the activated T lymphocytes might play an important role in the pathogenesis of SSc.

Research Products

• [Journal Article] Serum concentrations of Flt-3 ligand in rheumatic diseases (2015)
  • Author(s): Nakamura K, Nakatsuka N, Jinnin M, Makino T, Kajihara I, Makino K, Honda N, Inoue K, Fukushima S, Ihn H.
  • Journal Title: BioScience Trends Volume: 9 Issue: 5 Pages: 342-349
  • DOI: 10.5582/bst.2015.01121
  • NAID: 130005109609
  • ISSN: 1881-7815, 1881-7823
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced CCR9 expression levels in psoriatic skin are associated with poor clinical outcome to infliximab treatment. (2015)
  • Author(s): Koga A, Kajihara I, Yamada S, Makino K, Ichihara A, Aoi J, Makino T, Fukushima S, Jinnin M, Ihn H.
  • Journal Title: J Dermatol. Volume: 43 Issue: 5 Pages: 522-5
  • DOI: 10.1111/1346-8138.13178
  • Peer Reviewed / Open Access
• [Journal Article] EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin. (2015)
  • Author(s): Kudo H, Wang Z, Jinnin M, Nakayama W, Inoue K, Honda N, Nakashima T, Kajihara I, Makino K, Makino T, Fukushima S, Ihn H.
  • Journal Title: J Immunol. Volume: 195 Issue: 8 Pages: 3565-3573
  • DOI: 10.4049/jimmunol.1402362
  • Peer Reviewed / Open Access
• [Journal Article] Mice overexpressing integrin αv in fibroblasts exhibit dermal thinning of the skin. (2015)
  • Author(s): Wang Z, Jinnin M, Kobayashi Y, Kudo H, Inoue K, Nakayama W, Honda N, Makino K, Kajihara I, Makino T, Fukushima S, Inagaki Y, Ihn H.
  • Journal Title: J Dermatol Sci. Volume: 79 Issue: 3 Pages: 268-278
  • DOI: 10.1016/j.jdermsci.2015.06.008
  • Peer Reviewed / Open Access
• [Journal Article] Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients (2014)
  • Author(s): Takamitsu Makino; Masatoshi Jinnin; Mitsuhiko Etoh; Keitaro Yamane; Ikko Kajihara; Katsunari Makino; Asako Ichihara; Toshikatsu Igata; Keisuke Sakai; Satoshi Fukushima;
  • Journal Title: European Journal of Dermatology Volume: 24(4) Issue: 4 Pages: 760-6
  • DOI: 10.1684/ejd.2014.2384
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] MIRSNP rs2910164 of miR-146a is associated with the muscle involvement in polymyositis/dermatomyositis. (2013)
  • Author(s): Okada Y, Jinnin M, Makino T, Kajihara I, Makino K, Honda N, Nakayama W, Inoue K, Fukushima S, Ihn H.
  • Journal Title: International Journal of Dermatology Volume: 53 Pages: 300-304
  • Peer Reviewed
• [Journal Article] Proportion of Lymphocytic Inflammation with CD123 Positive Cells in Lupus Erythematous Profundus Predict a Clinical Response to Treatment. (2013)
  • Author(s): Miyashita A, Fukushima S, Makino T, Yoshino Y, Yamashita J, Honda N, Aoi J, Ichihara A, Jinnin M, Inoue Y, Ihn H.
  • Journal Title: Acta Dermato-Venereologica Volume: 17 Issue: 5 Pages: 563-567
  • DOI: 10.2340/00015555-1777
  • Peer Reviewed
• [Journal Article] Serum levels of tenascin-C in collagen diseases. (2013)
  • Author(s): Inoue K, Jinnin M, Hara Y, Makino K, Kajihara I, Makino T, Sakai K, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: Journal of Dermatology Volume: 40 Pages: 715-719
  • Peer Reviewed
• [Journal Article] Expression analysis of multiple microRNAs in each patient with scleroderma. (2013)
  • Author(s): Koba S, Jinnin M, Inoue K, Nakayama W, Honda N, Makino K, Kajihara I, Makino T, Fukushima S, Ihn H.
  • Journal Title: Experimental Dermatology Volume: 22 Issue: 7 Pages: 489-491
  • DOI: 10.1111/exd.12173
  • Peer Reviewed
• [Journal Article] Down-regulation of miR-223 contributes to the formation of Gottron's papules in dermatomyositis via the induction of PKCε (2013)
  • Author(s): Inoue K, Jinnin M, Yamane K, Makino T, Kajihara I, Makino K, Honda N, Nakayama W, Fukushima S, Ihn H.
  • Journal Title: European Journel of Dermatology Volume: 23 Issue: 2 Pages: 160-167
  • DOI: 10.1684/ejd.2013.1959
  • Peer Reviewed
• [Journal Article] The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma. (2013)
  • Author(s): Makino K, Jinnin M, Hirano A, Yamane K, Eto M, Kusano T, Honda N, Kajihara I, Makino T, Sakai K, Masuguchi S, Fukushima S, Ihn H.
  • Journal Title: Journal of Immunology Volume: 190 Issue: 8 Pages: 3905-3915
  • DOI: 10.4049/jimmunol.1200822
  • Peer Reviewed
• [Presentation] Increased CD27 expression in the skin and sera of the patients with systemic sclerosis. (2016)
  • Author(s): Takamitsu Makino, Masatoshi Jinnin, Miri Nakayama, Satoshi Fukushima, Shinichi Masuguchi, Hironobu Ihn
  • Organizer: 4th Systemic Sclerosis World Congress
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2016-02-18
  • Int'l Joint Research
• [Presentation] 限局性強皮症における血清および皮膚組織中miR-196aの発現低下とⅠ型コラーゲン蛋白合成の関連 (2015)
  • Author(s): 牧野貴充、神人正寿、江藤光彦、山根惠太郎、梶原一亨、牧野雄成、福島 聡、尹 浩信
  • Organizer: 第47回日本結合組織学会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-15
• [Presentation] 限局性強皮症における血清および皮膚組織中miR-196aの発現低下と線維化機序の関連 (2014)
  • Author(s): 牧野貴充、神人正寿、江藤光彦、山根惠太郎、梶原一亨、牧野雄成、福島 聡、尹 浩信
  • Organizer: 第42回臨床免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Effects of Sarpogrelate hydrochloride for Raynaud’s phenomenon secondary to systemic sclerosis (2014)
  • Author(s): Takamitsu Makino, Masatoshi Jinnin, Ikkou Kajihara, Katsunari Makino, Hironobu Ihn
  • Organizer: 3rd Systemic sclerosis World Congress
  • Place of Presentation: Rome