論文 - 詳細
| RRC ID | 88190 |
|---|---|
| 著者 | Le Texier L, Lineburg KE, Cao B, McDonald-Hyman C, Leveque-El Mouttie L, Nicholls J, Melino M, Nalkurthi BC, Alexander KA, Teal B, Blake SJ, Souza-Fonseca-Guimaraes F, Engwerda CR, Kuns RD, Lane SW, Teng M, Teh C, Gray D, Clouston AD, Nilsson SK, Blazar BR, Hill GR, MacDonald KP. |
| タイトル | Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease. |
| ジャーナル | JCI Insight |
| Abstract |
Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects in Tregs result in diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), a serious complication of allogeneic stem cell transplantation (SCT). We recently reported increased expression of autophagy-related genes (Atg) in association with enhanced survival of Tregs after SCT. Autophagy is a self-degradative process for cytosolic components that promotes cell homeostasis and survival. Here, we demonstrate that the disruption of autophagy within FoxP3+ Tregs (B6.Atg7fl/fl-FoxP3cre+ ) resulted in a profound loss of Tregs, particularly within the bone marrow (BM). This resulted in dysregulated effector T cell activation and expansion, and the development of enterocolitis and scleroderma in aged mice. We show that the BM compartment is highly enriched in TIGIT+ Tregs and that this subset is differentially depleted in the absence of autophagy. Moreover, following allogeneic SCT, recipients of grafts from B6.Atg7fl/fl-FoxP3cre+ donors exhibited reduced Treg reconstitution, exacerbated GVHD, and reduced survival compared with recipients of B6.WT-FoxP3cre+ grafts. Collectively, these data indicate that autophagy-dependent Tregs are critical for the maintenance of tolerance after SCT and that the promotion of autophagy represents an attractive immune-restorative therapeutic strategy after allogeneic SCT. |
| 巻・号 | 1(15) |
| ページ | e86850 |
| 公開日 | 2016-9-22 |
| DOI | 10.1172/jci.insight.86850 |
| PII | 86850 |
| PMID | 27699243 |
| PMC | PMC5033749 |
| MeSH | Animals Autophagy* Bone Marrow / physiopathology Female Graft vs Host Disease / immunology* Hematopoietic Stem Cell Transplantation Immune Tolerance Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes, Regulatory / immunology* |
| IF | 6.205 |
| 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 | |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| 実験動物マウス | RBRC02231 RBRC00806 |