Donor T-cell-derived interleukin-22 promotes thymus regeneration and alleviates chronic graft-versus-host disease in murine allogeneic hematopoietic cell transplant
Donor T-cell-derived interleukin-22 promotes thymus regeneration and alleviates chronic graft-versus-host disease in murine allogeneic hematopoietic cell transplant
复制标题
供体 T 细胞来源的白细胞介素 22 在小鼠同种异体造血细胞移植中促进胸腺再生并减轻慢性移植物抗宿主病
DOI：
10.1016/j.intimp.2018.12.023
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发表时间：
2019
影响因子：
5.6
通讯作者：
Xu Kailin
中科院分区：
文献类型：
--
作者：
Pan Bin;Zhang Fan;Lu Zhenzhen;Li Lingling;Shang Longmei;Xia Fan;Fu Ruixue;Xu Mengdi;Zeng Lingyu;Xu Kailin
胸腺缺陷会导致异基因造血细胞移植(allo-HCT)后移植后免疫功能恢复不良和免疫耐受功能障碍。促进胸腺再生是加速T细胞免疫恢复的潜在策略。据报道，IL-22参与了胸腺损伤后的再生。在本研究中，我们发现供者T细胞是异基因移植受者产生IL-22的主要来源。通过将IL-22基因敲除(IL-22ko)小鼠应用于allo-HCT，我们发现供者T细胞来源的IL-22促进胸腺再生与胸腺内IL-22水平升高有关。接受IL-22ko T细胞移植的受者表现出胸腺恢复不足，而注射外源性IL-22则逆转了这一现象。T细胞来源的IL-22在体外促进胸腺上皮细胞(TECs)增殖。此外，供者T细胞来源的IL-22增加了胸腺中Aire的表达水平，并降低了皮肤慢性移植物抗宿主病(GVHD)。此外，移植后短期使用外源性IL-22可以加速胸腺的恢复，而不会增加急性移植物抗宿主病的严重程度。我们的数据表明，T细胞和TECs之间的相互作用是介导异基因造血干细胞移植后T细胞免疫重建的重要机制。
Defect of thymus results in poor posttransplant immune recovery and dysfunction of immune tolerance after allogeneic hematopoietic cell transplants (allo-HCT). Improving thymus regeneration represents a potential strategy to accelerate recovery of T-cell immunity. IL-22 was reported to mediate thymus regeneration after injury. In this study, we found donor T-cell is a major source of IL-22 in allotransplant recipient. Through applying IL-22 knock out (IL-22KO) mice in allo-HCT, we found donor T-cell derived IL-22 promotes thymus regeneration in association with increased level of intra-thymic IL-22. IL-22KO T-cell-transplanted recipients show deficient thymus recovery which is reversed by injection of exogenous IL-22. T-cell derived IL-22 promotes proliferation of thymic epithelial cells (TECs) in vitro. In addition, donor T-cell derived IL-22 increases expression level of Aire in the thymus and decreases skin chronic graft-versus-host disease (GVHD). Furthermore, short-term use of exogenous IL-22 posttransplant accelerates recovery of thymus without increasing severity of acute GVHD. Our data indicate that cross-talk between T-cell and TECs is an important mechanism to mediate reconstitution of T-cell immunity after allo-HCT.