| RRC ID |
72814
|
| 著者 |
Hatano R, Itoh T, Otsuka H, Saeki H, Yamamoto A, Song D, Shirakawa Y, Iyama S, Sato T, Iwao N, Harada N, Aune TM, Dang NH, Kaneko Y, Yamada T, Morimoto C, Ohnuma K.
|
| タイトル |
Humanized anti-IL-26 monoclonal antibody as a novel targeted therapy for chronic graft-versus-host disease.
|
| ジャーナル |
Am J Transplant
|
| Abstract |
IL-26 is a Th17 cytokine, with its gene being absent in rodents. To characterize the in vivo immunological effects of IL-26 in chronic systemic inflammation, we used human IL26 transgenic (hIL-26Tg) mice and human umbilical cord blood mononuclear cells (hCBMC) in mouse allogeneic-graft-versus-host disease (GVHD) and chronic xenogeneic-GVHD model, respectively. Transfer of bone marrow and spleen T cells from hIL-26Tg mice into B10.BR mice resulted in GVHD progression, with clinical signs of tissue damage in multiple organs. IL-26 markedly increased neutrophil levels both in the GVHD-target tissues and peripheral blood. Expression levels of Th17 cytokines in hIL-26Tg mice-derived donor CD4 T cells were significantly increased, whereas IL-26 did not affect cytotoxic function of donor CD8 T cells. In addition, granulocyte-colony stimulating factor, IL-1β, and IL-6 levels were particularly enhanced in hIL-26Tg mice. We also developed a humanized neutralizing anti-IL-26 monoclonal antibody (mAb) for therapeutic use, and its administration after onset of chronic xenogeneic-GVHD mitigated weight loss and prolonged survival, with preservation of graft-versus-leukemia effect. Taken together, our data elucidate the in vivo immunological effects of IL-26 in chronic GVHD models and suggest that a humanized anti-IL-26 mAb may be a potential therapeutic agent for the treatment of chronic GVHD.
|
| 巻・号 |
22(12)
|
| ページ |
2804-2820
|
| 公開日 |
2022-12-1
|
| DOI |
10.1111/ajt.17178
|
| PMID |
35997569
|
| MeSH |
Animals
Antibodies, Monoclonal, Humanized / therapeutic use
Bone Marrow Transplantation
CD8-Positive T-Lymphocytes
Cytokines
Graft vs Host Disease* / drug therapy
Graft vs Host Disease* / etiology
Hematopoietic Stem Cell Transplantation*
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
|
| IF |
7.338
|
| リソース情報 |
| 研究用ヒト臍帯血幹細胞 |
|
