Identification and molecular dissection of pathological mechanisms in tissue injury of graft-versus-host disease
| Project/Area Number |
16K08743
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Sapporo Medical University |
|---|
Principal Investigator |
Kokai Yasuo 札幌医科大学, 医学部, 教授 (20178239)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
堀 司 札幌医科大学, 医学部, 准教授 (20398324)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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 | 造血幹細胞移植 / 移植片対宿主病 / 白血病 / 難病根治 / 組織適合抗原 / ドナー / バイオマーカー / 根治療法 / 分子標的療法 / GVHD / アロ移植 / 同種移植 / ケモカイン / CCL8 |
|---|
| Outline of Final Research Achievements |
Acute graft versus host disease (aGVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We previously reported that CC chemokine ligand 8 (CCL8), a member of CC chemokine family, is a potential candidate for the diagnostic and prognostic biomarker of aGVHD in human and mice as revealed by proteomic approach. Our study further suggested that the levels of plasma CCL8 is closely correlated with the severity and survival of aGVHD in mice. To elucidate a possible role of CCL8 in aGVHD pathology, we developed CCL8 knockout (CCL8KO) mice using zinc-finger nuclease and transplanted fully allogeneic grafts to CCL8KO mice. We found that CCL8 deficiency in hosts significantly reduces the early mortality of aGVHD and extends survival time significantly after lethal allogeneic HSCT. These findings indicate that CCL8 is intimately involved in mortality of aGVHD and could be a molecular candidate for aGVHD treatment.
|
| Academic Significance and Societal Importance of the Research Achievements |
造血幹細胞移植は血液悪性腫瘍などに対する根治的な治療法であり、その適応は先天性免疫不全や代謝疾患からがんなどの悪性固形腫瘍にまで多岐にわたっている。しかし重篤な合併症としての移植片対宿主病が造血幹細胞移植の成否に重大な影響をあたえ、移植片対宿主病のコントロールが造血幹細胞移植治療の成否を左右する。そのため移植片対宿主病の克服は造血幹細胞移植医療を安全かつ効果的に推進するために必須である。本研究により、今まで困難であった移植片対宿主病の早期客観診断が可能性が示唆された。さらに本研究で同定した分子は治療標的分子である可能性が示唆され、造血幹細胞移植の安全で有効な活用に重要な意義をもたらした。
|
Report
(4 results)
Research Products
(6 results)
-
-
[Journal Article] Early expression of serum CCL8 closely correlates to non-relapse mortality after allogeneic hematopoietic stem cell transplantation.2018
Author(s)
Yamamoto M, Hori T, Hatakeyama N, Igarashi K, Inazawa N, Suzuki N, Takei N, Ito Y-M, Matsumoto K, Kato K, Tsutsumi H, Kokai Y.
-
Journal Title
Sapporo Med J
Volume: 86
Pages: 45-51
NAID
Related Report
-
[Journal Article] HLA-A24 ligandome analysis of colon and lung cancer cells identifies a novel cancer-testis antigen and a neoantigen that elicits specific and strong CTL responses.2017
Author(s)
Kochin V, Kanaseki T, Tokita S, Miyamoto S, Shionoya Yo, Kikuchi Y, Morooka D, Hirohashi Y, Tsukahara T, Watanabe K, Toji S, Kokai Y, Sato N, Torigoe T.
-
Journal Title
Oncoimmunology
Volume: 6
Issue: 4
Pages: 1-12
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
