CD4+ CD52lo T-cell expression contributes to the development of systemic lupus erythematosus.

• Project/Area Number: 16K19604
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nagasaki University
• Principal Investigator: UMEDA Masataka 長崎大学, 病院(医学系), 助教 (20750053)
• Research Collaborator: KOGA Tomohiro 長崎大学, 医歯薬学総合研究科(医学系), 助教 (90537284) ; ICHINOSE Kunihiro 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60437895)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 全身性エリテマトーデス / CD52 / T細胞 / 免疫学 / 臨床 / マイクロアレイ

Outline of Final Research Achievements

The CD52 is widely expressed in lymphocytes. CD4+CD52hi T cells are functioning suppressor CD4+T cells. We investigated the role of the immune regulation of CD4+CD52 T cells in systemic lupus erythematosus (SLE). CD4+CD52lo T cells were increased in SLE patients, in positive correlation with SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular helper-like T cells (Tfh-like cells) were also increased in SLE, in positive correlation with CD4+CD52lo T cells. Chemokine receptor 8 (CCR8) expression in CD4+CD52lo T cells was increased. In vitro experiments using CD4 T cells of SLE patients showed that thymus and activation-regulated chemokine (TARC), a ligand of CCR8, contributed to the development of CD4+CD52hi T cells into CD4+CD52lo T cells. Our findings suggest that CD4+CD52lo T-cell upregulation is involved in the production of pathogens by autoantibodies, and TARC may contribute to the development of SLE through an aberrant induction of CD4+CD52lo T cells.

Research Products

• [Journal Article] CD4+ CD52lo T-cell expression contributes to the development of systemic lupus erythematosus. (2018)
  • Author(s): Umeda M, Koga T, Ichinose K(corresponding author), Igawa T, Sato T, Takatani A, Shimizu T, Fukui S, Nishino A, Horai Y, Hirai Y, Kawashiri SY, Iwamoto N, Aramaki T, Tamai M, Nakamura H, Yamamoto K, Abiru N, Origuchi T, Ueki Y, Kawakami A.
  • Journal Title: Clin Immunol. Volume: 187 Pages: 50-57
  • DOI: 10.1016/j.clim.2017.10.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The CD4+CD52low T cell Contributes to the Development of Systemic Lupus Erythematosus through the CCR8/TARC Pathway (2017)
  • Author(s): Umeda M, Koga T, Ichinose K, Igawa T, Kurushima S, Takatani A, Shimizu T, Fukui S, Nishino A, Horai Y, Kawashiri S, Iwamoto N, Hirai Y, Tamai M, Nakamura H, Origuchi T, Kawakami A
  • Organizer: Japan college of Rheumatology International Concurrent Workshop
  • Int'l Joint Research
• [Presentation] The CD4+CD52low Tcell contributes to Disease Activity and Autoantibody Production in Systemic Lupus Erythematosus (2016)
  • Author(s): M. Umeda, T. Koga, K. Ichinose, T. Michitsuji, T. Shimizu, S. Fukui, A. Nishino, Y. Nakashima, T. Suzuki, Y. Horai, Y. Hirai, S.-Y. Kawashiri, N. Iwamoto, T. Aramaki, M. Tamai , H. Nakamura , T. Origuchi , Y. Ueki , A. Kawakami
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: パシフィコ横浜 神奈川県横浜市
• [Presentation] The CD4+CD52low T Cell Contributes to the Development of Systemic Lupus Erythematosus through the CCR8/TARC Pathway (2016)
  • Author(s): T. Sato, M. Umeda, T. Koga, K. Ichinose, T. Igawa, S. Kurushima, T. Shimizu, S. Fukui, A. Nishino, Y. Horai, Y. Hirai, S.-Y. Kawashiri, N. Iwamoto, T. Aramaki, M. Tamai, H. Nakamura, T. Origuchi, Y. Ueki, A. Kawakami
  • Organizer: 2016アメリカリウマチ学会
  • Place of Presentation: アメリカ ワシントンDC
  • Int'l Joint Research