The role of regulatory B cell in systemic sclerosis and cytokine-induced fibrosis models

• Project/Area Number: 23591640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kanazawa University
• Principal Investigator: TAKEHARA KAZUHIKO 金沢大学, 医学系, 教授 (50142253)
• Co-Investigator(Kenkyū-buntansha): HASEGAWA Minoru 福井大学, 医学部, 教授 (50283130) ; MATSUSHITA Takashi 金沢大学, 大学病院, 講師 (60432126)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: IL-10 / B細胞 / 全身性強皮症 / 制御性B細胞

Research Abstract

Regulatory B cells that produce IL-10 are an important role for negative immune response. The frequency of regulatory B cell in PBMC from 28 systemic sclerosis patients and 24 healthy controls were examined. The frequency of regulatory B cell in PBMC was decreased in systemic sclerosis patients compared to healthy controls. Next, the role of regulatory B cell in the cytokine induced fibrosis models was examined using lack of regulatory B cell mice (CD19 deficient mice). There was no significant difference between wild type mice and CD19 deficient mice.These results suggest that decreased regulatory B cell may contribute to pathogenesis of systemic sclerosis, although regulatory B cell does not affect the development of fibrosis.

Research Products

• [Journal Article] Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody associated with diffuse cutaneous and skeletal muscle involvement. (2014)
  • Author(s): Kaji K, Fertig N, Medsger TA Jr, Satoh T, Hoshino K, Hamaguchi Y, Hasegawa M, Lucas M, Schnure A, Ogawa F, Sato S, Takehara K, Fujimoto M, Kuwana M.
  • Journal Title: Arthritis Care Res Volume: 66 Issue: 4 Pages: 575-84
  • DOI: 10.1002/acr.22163
  • Peer Reviewed
• [Journal Article] A crucial role of L-selectin in C protein-induced experimental polymyositis of mice. (2014)
  • Author(s): Oishi K, Hamaguchi Y, Matsushita T, Hasegawa M, Okiyama N, Dernedde J, Weinhart M, Haag R, Tedder TF, Takehara K, Kohsaka H, Fujimoto M.
  • Journal Title: Arthritis Rheumatol. Volume: mar 18 Issue: 7 Pages: 1864-71
  • DOI: 10.1002/art.38630
  • Peer Reviewed
• [Journal Article] The clinical characteristics of juvenile-onset systemic sclerosis in Japanese patients. (2014)
  • Author(s): Hatta Y, Hasegawa M, Matsushita T, Hamaguchi Y, Fujimoto M, Takehara K.
  • Journal Title: Mod Rheumatol. Volume: 24 Issue: 2 Pages: 377-9
  • DOI: 10.3109/14397595.2013.854073
  • Peer Reviewed
• [Journal Article] Serum adhesion molecule levels as prognostic markers in patients with early systemic sclerosis: a multicentre, prospective, observational study. (2014)
  • Author(s): Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H, Inoue K, Ishikawa O, Kawaguchi Y, Kuwana M, Ogawa F, Takahashi H, Tanaka S, Sato S, Takehara K.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: e88150-e88150
  • DOI: 10.1371/journal.pone.0088150
  • NAID: 120006986537
  • Peer Reviewed
• [Journal Article] High incidence of pulmonary arterial hypertension in systemic sclerosis patients with anti-centriole autoantibodies (2013)
  • Author(s): Hamaguchi Y, Matsushita T, Hasegawa M, Ueda-Hayakawa I, Sato S, Takehara K, Fujimoto M
  • Journal Title: Mod Rheumatol
  • Peer Reviewed
• [Journal Article] BLNK expression contributes to controlling allergic and autoimmune diseases by mediating IL-10 production in regulatory B cells (2013)
  • Author(s): Jin G, Hamaguchi Y, Matsushita T, Hasegawa M, Huu DL, Ishiura N, Naka K, Hirao A, Takehara K, Fujimoto M
  • Journal Title: J Allergy Clin Immunol Volume: 131 Issue: 6 Pages: 1674-1682
  • DOI: 10.1016/j.jaci.2013.01.044
  • Peer Reviewed
• [Journal Article] FTY720 ameliorates murine Scl-cGVHD by promoting expansion of splenic regulatory cells and inhibiting immune cell infiltration into skin (2013)
  • Author(s): Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M
  • Journal Title: Arthritis Rheum Volume: in press Issue: 6 Pages: 1624-35
  • DOI: 10.1002/art.37933
  • Peer Reviewed
• [Journal Article] Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease (2013)
  • Author(s): Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, T akehara K, T edder TF, Fujimoto M
  • Journal Title: Blood Volume: 121 Issue: 16 Pages: 3274-83
  • DOI: 10.1182/blood-2012-11-465658
  • Peer Reviewed
• [Journal Article] Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort. (2013)
  • Author(s): Fujimoto M
  • Journal Title: Ann Rheum Dis Volume: 72 Issue: 1 Pages: 151-153
  • DOI: 10.1136/annrheumdis-2012-201736
  • Peer Reviewed
• [Journal Article] Dermokine inhibits ELR(+)CXC chemokine expression and delays early skin wound healing. (2013)
  • Author(s): Hasegawa M, Higashi K, Matsushita T, Hamaguchi Y, Saito K, Fujimoto M, Takehara K.
  • Journal Title: J Dermatol Sci. Volume: 70 Issue: 1 Pages: 34-41
  • DOI: 10.1016/j.jdermsci.2013.01.007
  • Peer Reviewed
• [Journal Article] Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort. (2013)
  • Author(s): Fujimoto M, Matsushita T, Hamaguchi Y, Kaji K, Asano Y, Ogawa F, Yamaoka T, Fujikawa K, Tsukada T, Sato K, Echigo T, Hasegawa M, Takehara K.
  • Journal Title: Ann Rheum Dis. Volume: 72 Pages: 151-3
  • Peer Reviewed
• [Journal Article] Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease. (2013)
  • Author(s): Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, Takehara K, Tedder TF, Fujimoto M.
  • Journal Title: Blood Volume: in press
  • Peer Reviewed
• [Journal Article] FTY720 ameliorates murine Scl-cGVHD by promoting expansion of splenic regulatory cells and inhibiting immune cell infiltration into skin. (2013)
  • Author(s): Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M.
  • Journal Title: Arthritis Rheum Volume: in press
  • Peer Reviewed
• [Journal Article] Potential roles of interleukin 17A in the development of skin fibrosis (2012)
  • Author(s): Okamoto Y, Hasegawa M, Matsushita T, Hamaguchi Y, Huu DL, Iwakura Y, Fujimoto M, T akehara K
  • Journal Title: Arthritis Rheum Volume: 64 Issue: 11 Pages: 3726-35
  • DOI: 10.1002/art.34643
  • Peer Reviewed
• [Journal Article] Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies : possible association with malignancy (2012)
  • Author(s): Ichimura Y, Matsushita T, Hamaguchi Y, Kaji K, Hasegawa M, Tanino Y, Inokoshi Y, Kawai K, Kanekura T, Habuchi M, Igarashi A, Sogame R, Hashimoto T, Koga T, Nishino A, Ishiguro N, Sugimoto N, Aoki R, Ando N, Abe T, Kanda T, Kuwana M, Takehara K, Fujimoto M
  • Journal Title: Ann Rheum Dis Volume: 71(5) Issue: 5 Pages: 710-3
  • DOI: 10.1136/annrheumdis-2011-200697
  • NAID: 120004442395
  • Peer Reviewed
• [Journal Article] Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins (2012)
  • Author(s): Fujimoto M, Hamaguchi Y, Kaji K, Matsushita T, Ichimura Y, Kodera M, Ishiguro N, Ueda-Hayakawa I, Asano Y, Ogawa F, Fujikawa K, Miyagi T, Mabuchi E, Hirose K, Akimoto N, Hatta N, Tsutsui K, Higashi A, Igarashi A, Seishima M, Hasegawa M, Takehara K
  • Journal Title: Arthritis Rheum Volume: 64(2) Issue: 2 Pages: 513-22
  • DOI: 10.1002/art.33403
  • Peer Reviewed
• [Journal Article] Investigation of prognostic factors for skin sclerosis and lung function in Japanese patients with early systemic sclerosis: a multicentre prospective observational study. (2012)
  • Author(s): Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H, Inoue K, Ishikawa O, Kawaguchi Y, Kuwana M, Muro Y, Ogawa F, Sasaki T, Takahashi H, Tanaka S, Takehara K, Sato S.
  • Journal Title: Rheumatology (Oxford) Volume: 51 Issue: 1 Pages: 129-133
  • DOI: 10.1093/rheumatology/ker333
  • Peer Reviewed
• [Journal Article] Host-derived MCP-1 and MIP-1αregulate protective anti-tumor immunity to localized and metastatic B16 melanoma (2012)
  • Author(s): Nakasone Y, Fujimoto M, Matsushita T, Hamaguchi Y, Huu DL, Yanaba M, Sato S, Takehara K, Hasegawa M
  • Journal Title: Am J Pathol Volume: 180(1) Issue: 1 Pages: 365-74
  • DOI: 10.1016/j.ajpath.2011.09.005
  • Peer Reviewed
• [Journal Article] Association of UBE2L3 polymorphisms with diffuse cutaneous systemic sclerosis in a Japanese population. (2012)
  • Author(s): Hasebe N, Kawasaki A, Ito I, Kawamoto M, Hasegawa M, Fujimoto M, Furukawa H, Tohma S, Sumida T, Takehara K, Sato S, Kawaguchi Y, Tsuchiya N.
  • Journal Title: Ann Rheum Dis. Volume: 71 Pages: 1259-60
  • Peer Reviewed
• [Journal Article] Potential roles of interleukin 17A in the development of skin fibrosis. (2012)
  • Author(s): Okamoto Y, Hasegawa M, Matsushita T, Hamaguchi Y, Huu DL, Iwakura Y, Fujimoto M, Takehara K.
  • Journal Title: Arthritis Rheum. Volume: 64 Pages: 3726-35
  • Peer Reviewed
• [Journal Article] PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population. (2012)
  • Author(s): Terao C, （他19人中、5番目）
  • Journal Title: Arthritis Rheum. Volume: 94 Pages: 443-9
  • Peer Reviewed
• [Journal Article] Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy. (2012)
  • Author(s): Ichimura Y
  • Journal Title: Ann Rheum Dis. Volume: 71 Pages: 710-3
  • Peer Reviewed
• [Journal Article] Investigation of prognostic factors for skin sclerosis and lung function in Japanese patients with early systemic sclerosis: a multicentre prospective observational study. (2012)
  • Author(s): Hasegawa M
  • Journal Title: Rheumatology Volume: 51 Pages: 129-33
  • Peer Reviewed
• [Journal Article] Host-derived MCP-1 and MIP-1α regulate protective anti-tumor immunity to localized and metastatic B16 melanoma. (2012)
  • Author(s): Nakasone Y
  • Journal Title: Am J Pathol. Volume: 180 Pages: 365-74
  • Peer Reviewed
• [Journal Article] Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. (2012)
  • Author(s): Fujimoto M
  • Journal Title: Arthritis Rheum. Volume: 64 Pages: 513-22
  • Peer Reviewed
• [Journal Article] Inducible costimulator (ICOS) and ICOS ligand signaling has pivotal roles in skin wound healing via cytokine production (2011)
  • Author(s): Maeda S, Fujimoto M, Matsushita T, Hamaguchi Y, Takehara K, Hasegawa M
  • Journal Title: Am J Pathol Volume: 179(5) Issue: 5 Pages: 2360-9
  • DOI: 10.1016/j.ajpath.2011.07.048
  • Peer Reviewed
• [Journal Article] Association between nail-fold capillary findings and disease activity in dermatomyositis (2011)
  • Author(s): Mugii N, Hasegawa M, Matsushita T, Hamaguchi Y, Horie S, Yahata T, Inoue K, Someya F, Fujimoto M, Takehara K
  • Journal Title: Rheumatology (Oxford) Volume: 50(6) Issue: 6 Pages: 1091-8
  • DOI: 10.1093/rheumatology/keq430
  • Peer Reviewed
• [Journal Article] Use of serum clara cell 16-kDa (CC16) levels as a potential indicator of active pulmonary fibrosis in systemic sclerosis (2011)
  • Author(s): Hasegawa M, Fujimoto M, Hamaguchi Y, Matsushita T, Inoue K, Sato S, Takehara K
  • Journal Title: J Rheumatol Volume: 38(5) Issue: 5 Pages: 877-84
  • DOI: 10.3899/jrheum.100591
  • Peer Reviewed
• [Journal Article] Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study. (2011)
  • Author(s): Hamaguchi Y, Kuwana M, Hoshino K, Hasegawa M, Kaji K, Matsushita T, Komura K, Nakamura M, Kodera M, Suga N, Higashi A, Ogusu K, Muro Y, et al. （全37名中17番目）
  • Journal Title: Arch. Dermatol. Volume: 147 Issue: 4 Pages: 391-398
  • DOI: 10.1001/archdermatol.2011.52
  • Peer Reviewed
• [Journal Article] Inducible costimulator (ICOS) and ICOS ligand signaling has pivotal roles in skin wound healing via cytokine production. (2011)
  • Author(s): Maeda S
  • Journal Title: Am J Pathol. Volume: 179 Pages: 2360-9
  • Peer Reviewed
• [Journal Article] Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study. (2011)
  • Author(s): Hamaguchi Y
  • Journal Title: Arch Dermatol. Volume: 147 Pages: 391-8
  • Peer Reviewed
• [Journal Article] Association between nail-fold capillary findings and disease activity in dermatomyositis. (2011)
  • Author(s): Mugii N
  • Journal Title: Rheumatology Volume: 50 Pages: 1091-8
  • Peer Reviewed
• [Presentation] T Cyclosporine-Therapy in localozed scleroderma (2014)
  • Author(s): Takehara K
  • Organizer: 3rd World Congress on Systemic Sclerosis
  • Place of Presentation: Roma Italy : Ergife Palace Hotel & Conference Center
  • Year and Date: 2014-02-06
  • Invited
• [Presentation] アトピー性皮膚炎診療が楽しくなる～小児における実践治療を中心に～ (2012)
  • Author(s): 竹原和彦
  • Organizer: 第25回近畿小児科学会
  • Place of Presentation: キャンパスプラザ京都
  • Year and Date: 2012-03-11
  • Invited
• [Presentation] 豚原病を診る若手医師の育成を目指して (2012)
  • Author(s): 竹原和彦
  • Organizer: 第111回日本皮膚科学会総会
  • Place of Presentation: 京都国際会館(特別発言)
  • Invited
• [Presentation] アトピービジネス問題再考 (2012)
  • Author(s): 竹原和彦
  • Organizer: 第111回日本皮膚科学会総会
  • Place of Presentation: 京都市、国立京都国際会館
  • Invited
• [Presentation] 特別発言～膠原病を診る若手医師の育成を目指して～ (2012)
  • Author(s): 竹原和彦
  • Organizer: 第111回日本皮膚科学会総会
  • Place of Presentation: 京都市、国立京都国際会館
  • Invited
• [Presentation] アトピー性皮膚炎診療が楽しくなる～小児における実践治療を中心に～ (2012)
  • Author(s): 竹原和彦
  • Organizer: 第25回近畿小児科学会(招待講演)
  • Place of Presentation: 京都、キャンパスプラザ
• [Presentation] びまん型全身性強皮症に対するIVIGの三重盲検比較試験 (2011)
  • Author(s): 竹原和彦
  • Organizer: 第39回日本臨床免疫学会総会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2011-09-15
• [Presentation] びまん型全身性強皮症に対するIVIGの二重盲検比較試験 (2011)
  • Author(s): 竹原和彦
  • Organizer: 第39回日本臨床免疫学会総会
  • Place of Presentation: 東京、京王プラザホテル
• [Presentation] T Cyclosporine-Therapy in localozed scleroderma
  • Author(s): Takehara K
  • Organizer: 3rd World Congress on Systemic Sclerosis
  • Place of Presentation: Roma Italy
  • Invited
• [Presentation] 内科医が知っておくべき皮膚疾患／ｱﾄﾋﾟｰ性皮膚炎（教育講演）
  • Author(s): 竹原和彦
  • Organizer: 第27回日本臨床内科医学会
  • Place of Presentation: 神戸 神戸国際会議場
  • Invited
• [Presentation] アトピー性皮膚炎治療におけるガイドラインの役割（ワークショップ）
  • Author(s): 竹原和彦
  • Organizer: アトピー性皮膚炎治療研究会第19回シンポジム
  • Place of Presentation: 広島 広島大学医学部広仁会館
  • Invited
• [Book] アトピー性皮膚炎診療が楽しくなる!Q&Aで考える実践治療 (2011)
  • Author(s): 竹原和彦
  • Publisher: 南江堂
• [Book] 皮膚科臨床アセット、アトピー性皮膚炎の疫学 (2011)
  • Author(s): 竹原和彦
  • Total Pages: 4
  • Publisher: 中山書店
• [Book] 皮膚科臨床アセット、アトピー性皮膚炎の診断基準，鑑別診断 (2011)
  • Author(s): 伊川友香，竹原和彦
  • Total Pages: 5
  • Publisher: 中山書店
• [Book] 皮膚疾患の最新治療 (2011)
  • Author(s): 竹原和彦
  • Total Pages: 1
  • Publisher: 南江堂
• [Book] 皮膚科膠原病診療のすべて (2011)
  • Author(s): 竹原和彦
  • Total Pages: 3
  • Publisher: 南江堂
• [Book] アトピー性皮膚炎診療が楽しくなる！Q＆Aで考える実践治療 (2011)
  • Author(s): 竹原和彦
  • Total Pages: 212
  • Publisher: 南江堂