| Project/Area Number |
16H05201
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
Inui Masanori
Itou Ari
Endo Shota
Su Mei-Tzu
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
|---|
| Keywords | 免疫抑制 / 免疫チェックポイント / レセプター / 自己免疫疾患 / 免疫寛容 / 全身性エリテマトーデス / 皮膚筋炎 / LILRファミリー / 形質細胞 / 抗体療法 / 免疫抑制分子 / 自己抗体 / 病原性プラズマセル / 免疫抑制受容体 |
|---|
| Outline of Final Research Achievements |
In this study, first we have found that expression of leukocyte immunoglobulin-like receptor (LILR)B4, an inhibitory member of the human LILR family, is augmented in autoantibody-producing plasmablasts/plasma cells (PCs) of systemic lupus erythematosus (SLE) patients. However, the mechanism behind the upregulation of LILRB4 upon pathogenic antibody-secreting cells is yet to be known. To clarify the mechanism, next we have examined if glycoprotein 49B (gp49B), the murine counterpart of human LILRB4, is also elevated in autoantibody-producing cells in several SLE mouse models. We have found that gp49B is indeed expressed on PC of SLE-prone models but not of healthy C57BL/6 mice, and the level was positively correlated to the autoantibody IgG titer in serum. Gp49B genetic deletion, however, did not abolish the serum autoantibodies or fully ameliorate the lethal glomerulonephritis, indicating that gp49B is not the sole regulator of lupus but a pathogenic element in the disease.
|
| Academic Significance and Societal Importance of the Research Achievements |
SLEではステロイド剤と免疫抑制剤を併用することで短期生存率が著明に改善しているが特異性に乏しく，ステロイド長期投与による骨粗鬆症や感染症，動脈硬化性病変などは長期の生命予後，患者QOLを大きく低下させる。自己抗体のソースである汎B・活性化Bリンパ球を標的にした抗体療法の臨床試験が進められているが，リスク，ベネフィットのバランスに優れた薬剤の開発は成功していない。本研究は自己抗体を高産生するSLE病原性プラズマセル（PC）特異的に高発現する，リガンドが未同定のオーファン受容体LILRB4（B4）を見出した。これにより病原性PC特異的に治療する道筋が見えた。
|
