Reference - Detail
| RRC ID | 72814 |
|---|---|
| Author | 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. |
| Title | Humanized anti-IL-26 monoclonal antibody as a novel targeted therapy for chronic graft-versus-host disease. |
| Journal | 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. |
| Volume | 22(12) |
| Pages | 2804-2820 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Cord blood stem cells for research | |