論文 - 詳細
| RRC ID | 36671 |
|---|---|
| 著者 | Ohnuma K, Hatano R, Aune TM, Otsuka H, Iwata S, Dang NH, Yamada T, Morimoto C. |
| タイトル | Regulation of pulmonary graft-versus-host disease by IL-26+CD26+CD4 T lymphocytes. |
| ジャーナル | J Immunol |
| Abstract |
Obliterative bronchiolitis is a potentially life-threatening noninfectious pulmonary complication after allogeneic hematopoietic stem cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In the current study, we identified a novel effect of IL-26 on transplant-related obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγ(null) mice transplanted with human umbilical cord blood (HuCB mice) gradually developed clinical signs of graft-versus-host disease (GVHD) such as loss of weight, ruffled fur, and alopecia. Histologically, lung of HuCB mice exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26(+)CD26(+)CD4 T cells. Concomitantly, skin manifested fat loss and sclerosis of the reticular dermis in the presence of apoptosis of the basilar keratinocytes, whereas the liver exhibited portal fibrosis and cholestasis. Moreover, although IL-26 is absent from rodents, we showed that IL-26 increased collagen synthesis in fibroblasts and promoted lung fibrosis in a murine GVHD model using IL-26 transgenic mice. In vitro analysis demonstrated a significant increase in IL-26 production by HuCB CD4 T cells following CD26 costimulation, whereas Ig Fc domain fused with the N-terminal of caveolin-1 (Cav-Ig), the ligand for CD26, effectively inhibited production of IL-26. Administration of Cav-Ig before or after onset of GVHD impeded the development of clinical and histologic features of GVHD without interrupting engraftment of donor-derived human cells, with preservation of the graft-versus-leukemia effect. These results therefore provide proof of principle that cGVHD of the lungs is caused in part by IL-26(+)CD26(+)CD4 T cells, and that treatment with Cav-Ig could be beneficial for cGVHD prevention and therapy. |
| 巻・号 | 194(8) |
| ページ | 3697-712 |
| 公開日 | 2015-4-15 |
| DOI | 10.4049/jimmunol.1402785 |
| PII | jimmunol.1402785 |
| PMID | 25786689 |
| PMC | PMC4568737 |
| MeSH | Animals CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / pathology Caveolin 1 / genetics Caveolin 1 / pharmacology Cord Blood Stem Cell Transplantation* Dermis / immunology Dermis / pathology Dipeptidyl Peptidase 4 / genetics Dipeptidyl Peptidase 4 / immunology* Graft vs Host Disease / genetics Graft vs Host Disease / immunology* Graft vs Host Disease / pathology Graft vs Leukemia Effect / genetics Humans Interleukins / genetics Interleukins / immunology* Lung / immunology* Lung / pathology Lung Diseases / genetics Lung Diseases / immunology* Lung Diseases / pathology Mice Mice, Inbred NOD Mice, Knockout NIH 3T3 Cells Receptors, Fc / genetics Receptors, Fc / immunology Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / immunology |
| IF | 4.886 |
| 引用数 | 19 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 研究用ヒト臍帯血幹細胞 | 研究用ヒト臍帯血幹細胞 |
| ヒト・動物細胞 | NIH3T3 |