The role of immunosuppressive receptor LILRB in the pathogenesis of Kawasaki disease, and its application to the therapy.

• Project/Area Number: 26461597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Department of Clinical Research, National Hospital Organization Sendai Medical Center
• Principal Investigator: Kumaki Satoru 独立行政法人国立病院機構(仙台医療センター臨床研究部), その他部局等, 部長 (20311566)
• Co-Investigator(Kenkyū-buntansha): 高井 俊行 東北大学, 加齢医学研究所, 教授 (20187917) ; 乾 匡範 東北大学, 加齢医学研究所, 講師 (80443985)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 川崎病 / 免疫抑制性受容体 / LILRB4 / 免疫グロブリン大量療法 / plasmablast / LILRB

Outline of Final Research Achievements

Kawasaki disease (KD) is an acute vasculitis of unknown pathogenesis which occurs most frequently in early childhood, and intravenous immunoglobulin (IVIG) is effective. To obtain a mechanistic insight into the humoral immune response in KD patients, B cell subpopulations and the expression pattern of immunosuppressive receptor LILRB was analyzed. As a result, proportion of memory B cells increased in acute phase of the KD patients when compared with normal controls. Furthermore, the proportion of plasmablasts was significantly elevated in the acute phase of KD, which returned to the basal level after IVIG. From these results, it was suggested that adaptive immunity is involved in the pathogenesis of KD. In addition, we demonstrate that the expression of LILRB4 was enhanced in the acute phase of KD, and the expression was controlled by IVIG. These results suggest that plasmablasts with increased LILRB4 expression play an important role in the pathogenesis of KD.

Research Products

• [Journal Article] EXPLORING OF IMMUNE INHIBITORY RECEPTORS THAT CHARACTERIZE PATHOGENIC PLASMA CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS (2017)
  • Author(s): Takai T, Inui M.
  • Journal Title: Japanese Journal of Allergology Volume: 66 Issue: 1 Pages: 27-31
  • DOI: 10.15036/arerugi.66.27
  • NAID: 130005394544
  • ISSN: 0021-4884, 1347-7935
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Co-circulation of Enteroviru-D68, Human Rhinoviruses, and Respiratory Syncytial Virus among Children in Sendai, Japan. (2017)
  • Author(s): Metoki T, Okamoto M, Suzuki A, Kitaoka S, Miyabayashi H, Rokugo Y, Onuma R, Noguchi R, Sato T, Watanabe Y, Ohmiya S, Sato K, Nishimura H, Oshitani H, Kumaki S.
  • Journal Title: Pediatr Infect Dis J. Volume: -
  • Peer Reviewed
• [Journal Article] A nationwide survey of common viral infections in childhood among patients with primary immunodeficiency diseases. (2016)
  • Author(s): 12.Nanishi E, Hoshina T, Takada H, Ishimura M, Nishio H, Uehara T, Mizuno Y, Hasegawa S, Ohga S, Nagao M, Igarashi M, Yajima S, Kusumoto Y, Onishi N, Sasahara Y, Yasumi T, Heike T, Hara T, Kumaki S, et al.;
  • Journal Title: J Infect. Volume: 73 Issue: 4 Pages: 358-368
  • DOI: 10.1016/j.jinf.2016.07.018
  • Peer Reviewed
• [Journal Article] A Term Infant of Neonatal Toxic Shock Syndrome-Like Exanthematous Disease Complicated with Hemophagocytic Syndrome (2016)
  • Author(s): Kaga A, Watanabe H, Miyabayashi H, Metoki T, Kitaoka S, Kumaki S.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 240 Issue: 2 Pages: 167-170
  • DOI: 10.1620/tjem.240.167
  • NAID: 130005431536
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE. (2016)
  • Author(s): Inui M, Sugahara-Tobinai A, Fujii H, Itoh-Nakadai A, Fukuyama H, Kurosaki T, Ishii T, Harigae H, Takai T.
  • Journal Title: Int Immunol. Volume: Dec;28(12) Issue: 12 Pages: 597-604
  • DOI: 10.1093/intimm/dxw044
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Perinatal Coxsackievirus B3 Infection with Transient Thrombocytopenia (2016)
  • Author(s): Kaga A, Katata Y, Suzuki A, Otani K, Watanabe H, Kitaoka S, Kumaki S.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 239 Issue: 2 Pages: 135-138
  • DOI: 10.1620/tjem.239.135
  • NAID: 130005154460
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Transient Creatine Kinase Elevation Followed by Hypocomplementemia in a Case of Rotavirus Myositis. (2016)
  • Author(s): Rokugo Y, Kumaki S, Onuma R, Noguchi R, Suzuki S, Kusaka N, Watanabe Y, Kitaoka S.
  • Journal Title: Case Rep Pediatr. Volume: 2016 Pages: 3034170-3034170
  • DOI: 10.1155/2016/3034170
  • Peer Reviewed / Open Access
• [Journal Article] A late presenter and long-term survivor of alveolar capillary dysplasia with misalignment of the pulmonary veins. (2015)
  • Author(s): Ito Y, Akimoto T, Cho K, Yamada M, Tanino M, Dobata T, Kitaichi M, Kumaki S, Kinugawa Y
  • Journal Title: Eur J Pediatr Volume: 174 Issue: 8 Pages: 1123-6
  • DOI: 10.1007/s00431-015-2543-3
  • Peer Reviewed
• [Journal Article] Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses. (2015)
  • Author(s): Kimura T, Endo S, Inui M, Saitoh S, Miyake K, Takai T.
  • Journal Title: J Immunol. Volume: 194 Issue: 11 Pages: 5426-5436
  • DOI: 10.4049/jimmunol.1402006
  • Peer Reviewed / Open Access
• [Journal Article] Platelets convert peripheral blood circulating monocytes to regulatory cells via immunoglobulin G and activating-type Fcγ receptors. (2015)
  • Author(s): Inui M, Tazawa K, Kishi Y, Takai T.
  • Journal Title: BMC Immunol. Volume: 16 Issue: 1 Pages: 20-20
  • DOI: 10.1186/s12865-015-0086-z
  • Peer Reviewed / Open Access
• [Journal Article] Human CD43+ B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally in healthy individuals. (2015)
  • Author(s): Inui M, Hirota S, Hirano K, Fujii H, Sugahara-Tobinai A, Ishii T, Harigae H, Takai T
  • Journal Title: Internationa Immunology Volume: 27 Issue: 7 Pages: 345-55
  • DOI: 10.1093/intimm/dxv009
  • Peer Reviewed / Open Access
• [Journal Article] Immune complexes regulate bone metabolism through FcRγ signalling (2015)
  • Author(s): Negishi-Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu A, Suda T, Sato K, Takai T, Takayanagi H.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 6637-6637
  • DOI: 10.1038/ncomms7637
  • Peer Reviewed / Open Access
• [Journal Article] A DAP12-Dependent Signal Promotes Pro-Inflammatory Polarization in Microglia Following Nerve Injury and Exacerbates Degeneration of Injured Neurons. (2015)
  • Author(s): Kobayashi M, Konishi H, Takai T, Kiyama H.
  • Journal Title: Glia Volume: 63 Issue: 6 Pages: 1073-1082
  • DOI: 10.1002/glia.22802
  • Peer Reviewed / Open Access
• [Journal Article] Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases (2015)
  • Author(s): Kanno A, Tanimura N, Ishizaki M, Ohko K, Motoi Y, Onji M, Fukui R, Shimozato T, Yamamoto K, Shibata T, Sano S, Sugahara-Tobinai A, Takai T, Ohto U, Shimizu T, Saitoh S, Miyake K.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6119-6119
  • DOI: 10.1038/ncomms7119
  • Peer Reviewed / Open Access
• [Journal Article] Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome. (2014)
  • Author(s): Horino S, Sasahara Y, Sato M, Niizuma H, Kumaki S, Abukawa D, Sato A, Imaizumi M, Kanegane H, Kamachi Y, Sasaki S, Terui K, Ito E, Kobayashi I, Ariga T, Tsuchiya S, Kure S.
  • Journal Title: Pediatr Transplant Volume: 18
  • Peer Reviewed
• [Journal Article] Life-threatening QT prolongation in a boy with attention-deficit/hyperactivity disorder on atomoxetine. (2014)
  • Author(s): Yamaguchi H, Nagumo K, Nakashima T, Kinugawa Y, Kumaki S.
  • Journal Title: Eur J Pediatr Volume: 173 Pages: 1631-4
  • Peer Reviewed
• [Journal Article] The open conformation of WASP regulates its nuclear localization and gene transcription in myeloid cells. (2014)
  • Author(s): 2.Looi CY, Sasahara Y, Watanabe Y, Sato M, Hakozaki I, Uchiyama M, Wong WF, Uchiyama T, Kumaki S, Tsuchiya S, Kure S
  • Journal Title: International Immnology Volume: 26 Issue: 6 Pages: 341-352
  • DOI: 10.1093/intimm/dxt072
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of acute cerebellitis with a unique sequential change on MRI. (2014)
  • Author(s): Suzuki S, Kaga A, Kusaka N, Uematsu M, Haginoya, Katata Y, Matsubara Y, Ishida T, Kitaoka S, Kumaki S.
  • Journal Title: Pediatr Neurol Volume: 51 Issue: 2 Pages: 279-81
  • DOI: 10.1016/j.pediatrneurol.2014.05.002
  • Peer Reviewed
• [Presentation] 川崎病患者に対する免疫グロブリン大量療法前後における抑制性受容体LILRB発現の変化について. (2016)
  • Author(s): 久間木悟、乾匡範、飛内章子、三浦舞子、目時嵩也、渡邊庸平、大沼良一、野口理恵、貴田岡節子、高井俊行.
  • Organizer: 第36回日本川崎病学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-01