Induction of regulatory T eel Is by SHPS-1/SIRPα-related proteins and regulation of skin inflammation

• Project/Area Number: 19591307
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kobe University
• Principal Investigator: HORIKAWA Tatsuya Kobe University, 医学研究科, 准教授 (00173633)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Ryuji 独立行政法人国立病院機構(相模原病院臨床研究センター), 臨床研究センター・診断治療研究室, 研究室長 (70373470)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 樹状細胞 / SHPS-1 / 細胞遊走 / Rho kinase / XS52 / 抗SHPS-1抗体 / SHPS-1 knockoutマウス / fasudil / MIP3β / 免疫寛容 / 接触過敏症

Research Abstract

マウスに抗SHPS-1抗体を投与することによって接触過敏症の抑制を誘導できたが、ハプテン特異的免疫寛容を誘導できなかった。CCR7刺激による皮膚樹状細胞の遊走はRho kinaseの活性化を伴っており、抗SHPS-1抗体によってCCR7による遊走およびRho kinaseの活性化は抑制された。またSHPS-1変異マウスの骨髄から作成した樹状細胞はCCR7刺激による遊走が現弱していた。これらのことよりSHPS-1は感作相において接触過敏症を制御するが、その機序はRho kinaseを介したCCR7刺激による遊走の制御によるものであることが示唆された。

Research Products

• [Journal Article] Thioredoxin Suppresses the Contact Hypersensitivity Response by Inhibiting Leukocyte Recruitment during the Elicitation Phase (2009)
  • Author(s): Fukunaga A, Horikawa T, et al, 他8名
  • Journal Title: Antioxid Redox Signal (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Impact of the Gly573Ser substitution in TRPV3 on the developmentof allergic and pruritic dermatitis in mice (2009)
  • Author(s): Yoshioka T, Horikawa T, et al, 他7名
  • Journal Title: J Invest Dermatol 129 Pages: 714-722
  • Peer Reviewed
• [Journal Article] Impact of the Gly573Ser substitution in TRPV3 on the development of allergic and pruitic dermatitis in mice. (2009)
  • Author(s): Yoshioka T, Imura K, Akasawa M, Suzuki M, Oshima I, Hirasawa T, Sakata T, Horikawa T, Arimura A
  • Journal Title: J Invest Dermatol 129 Pages: 714-722
  • Peer Reviewed
• [Journal Article] Thioredoxin Suppresses the Contact Hypersensitivity Response by Inhibiting Leukocyte Recruitment during the Elicitation Phase. (2009)
  • Author(s): Fukunaga A, Horikawa T, Ogura K, Taguchi K, Yu X, Funasaka Y, Takeda M, Nakamura H, Yodoi J, Nishigori C
  • Journal Title: Antioxid Redox Signal (In press (Epub ahead of print))
  • Peer Reviewed
• [Journal Article] Association of T-cell receptor Vbeta haplotypes with dry skin in DS-Nh mice (2008)
  • Author(s): Imura K, Horikawa T, et al, 他6名
  • Journal Title: Clin Exp Dermatol 34 Pages: 61-67
  • Peer Reviewed
• [Journal Article] Inhibition of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 reduces the severity of collagen-induced arthritis (2008)
  • Author(s): Tanaka K, Horikawa T, Suzuki R, et al, 他9名
  • Journal Title: J Rheumatol. 35 Pages: 2316-2324
  • Peer Reviewed
• [Journal Article] Skew in T cell receptor usage with polyclonal expansion in lesions of oral lichen planus without hepatitis C virus infection (2008)
  • Author(s): Gotoh A, Horikawa T, et al,
  • Journal Title: Clin Exp Immunol. 154 Pages: 192-201
  • Peer Reviewed
• [Journal Article] Blockade of collagen-induced arthritis post-onset by antibody to SRC homology 2 domain-containing protein tyrosine phosphatase substrate-1. (2008)
  • Author(s): Tanaka K, Kitaura K, Suzuki S, Watanabe J, Gotoh A, Shiobara N, Yamane S, Fukui N, Horikawa T, Suzuki R, Ochi T
  • Journal Title: J Rheumatol 35 Pages: 2316-2324
  • Peer Reviewed
• [Journal Article] Association of T-cell receptor Vbeta haplotypes with dry skin in DS-Nh mice. (2008)
  • Author(s): Imura K, Yoshioka T, Hikita I, Hirasawa T, Sakata T, Matsutani T, Horikawa T, Arimura A
  • Journal Title: Clin Exp Dermatol, 34:61-67, 2008 34 Pages: 61-67
  • Peer Reviewed
• [Journal Article] Polyclonal expansion of T cells bearing restricted T cell receptor repertoires in lesions of oral lichen planus without hepatitis C virus infection. (2008)
  • Author(s): GotoΛ, Hamada Y, Shiobara N, Kumagai K, Seto K, Horikawa T, Suzuki R
  • Journal Title: Clin Exp Immunol 154 Pages: 192-201
  • Peer Reviewed
• [Journal Article] Allergic contact dermatitis caused by poly(adipic acid-co-1,2-propylene glycol) and di-(n-octyl)tin-bis(2-ethylhexylmaleate) in vinyl chloride gloves (2007)
  • Author(s): Ueno M, Horikawa T, et al, 他4名
  • Journal Title: Contact Dermatitis 57 Pages: 349-351
  • Peer Reviewed
• [Journal Article] Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome (2007)
  • Author(s): Tohyama M, Horikawa T, et al, 他4名
  • Journal Title: Br J Dermatol 157 Pages: 934-940
  • Peer Reviewed
• [Journal Article] Impact of T-cell receptor Vb haplotypes on the development of dermatitis in DS-Nh mice: synergistic production of interleukin-13 caused by staphyloccal enterotoxin C and peptide glycans from Staphylococcus aureus (2007)
  • Author(s): Yoshioka T, Horikawa T, et al, 他6名
  • Journal Title: Immunology 121 Pages: 51-56
  • Peer Reviewed
• [Journal Article] Bacterial superantigens and T cell receptor β-chain-bearing T cells in the immunopathogenesis of ulcerative colitis (2007)
  • Author(s): Shiobara N, Suzuki R, et al, 他9名
  • Journal Title: Clin Exp Immunol 150 Pages: 13-21
  • Peer Reviewed
• [Journal Article] Impact of T-cell receptor Vβhaplotypes on the development of dermatitis in DS-Nh mice: synergistic production of interleukin-13 caused by staphyloccal enterotoxin C and peptide glycans from Staphylococcus aureus. (2007)
  • Author(s): Yoshioka T, Imura K, Hikita I, Hirasawa T, Sakata T, Matsutani T, Horikawa T, Arimura A
  • Journal Title: lmmunology 121 Pages: 51-56
  • Peer Reviewed
• [Journal Article] Allergic contact dermatitis due to poly(adipic acid-co-1, 2-propylene glycol)and di(n-octyl)tin-bis(2-ethylhexylmaleate)in the vinyl chloride gloves. (2007)
  • Author(s): Ueno M, Adachi A, Horikawa T, Inoue N, Mori A, Sasaki K
  • Journal Title: Contact Dermatitis 57 Pages: 349-351
  • Peer Reviewed
• [Journal Article] Bacterial superantigens and T cell receptor β-chain-bearing T cells in the immunopathogenesis of ulcerative colitis. (2007)
  • Author(s): Shiobara N, Suzuki Y, Aoki H, Gotoh A, Fujii Y, Hamada Y, Suzuki S, Fukui N, Kurane I, Itoh T, Suzuki R.
  • Journal Title: Clin Exp Immunol 150 Pages: 13-21
  • Peer Reviewed
• [Presentation] CCR7-mediated migration of DCs through activation of Rho kinase is regulated by SHPS-1 (2008)
  • Author(s): Horikawa T, Ogura K, et al, 他6名
  • Organizer: 10th International Meeting on Dendritic Cells
  • Place of Presentation: Kobe
• [Presentation] CCR7-mediated migration of dendritic cells through activation of Rho kinase is regulated by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (2008)
  • Author(s): Ogura K, Horikawa T, et al
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Kyoto
• [Presentation] 樹状細胞のCCR7刺激によるrho kinaseの活性化におけるSHPS-1の制御 (2008)
  • Author(s): 堀川達弥, 小倉香奈子, 他5名
  • Organizer: 日本皮膚科学会総会
  • Place of Presentation: 京都
• [Presentation] CCR7-mediated migration of dendritic cells through activation of Rho kinase is regulated by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (2008)
  • Author(s): Ogura K, Oniki s, Fukunaga A, Nagai H, Okazawa H, Matozaki T, Nishigori C, Horikawa T
  • Organizer: International Investigative Dermatology2008
  • Place of Presentation: Kyoto
• [Presentation] Rho kinase plays a crutial role in the migration of epidermal Langerhans cells mediated by CCR7 (2007)
  • Author(s): Oniki T, Horikawa T, et al, 他5名
  • Organizer: 日本研究皮膚科学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-04-19
• [Presentation] Rho kinase plays a crutial role in the migration of epidermal Langerhans cells mediated by CCR7. (2007)
  • Author(s): Oniki T, Fukunaga A, Nagai H, Yu X, Ogura K, Nishigori C, Horikawa T
  • Organizer: 日本研究皮膚科学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-04-19