Bruce Danny W, Stefanski Heather E, Vincent Benjamin G, Dant Trisha A, Reisdorf Shannon, Bommiasamy Hemamalini, Serody David A, Wilson Justin E, McKinnon Karen P, Shlomchik Warren D, Armistead Paul M, Ting Jenny P Y, Woosley John T, Blazar Bruce R, Zaiss Dietmar M W, McKenzie Andrew N J, Coghill James M, Serody Jonathan S
J Clin Invest. 2017 May 1;127(5):1813-1825. doi: 10.1172/JCI91816. Epub 2017 Apr 4.
Acute graft-versus-host disease (aGVHD) is the most common complication for patients undergoing allogeneic stem cell transplantation. Despite extremely aggressive therapy targeting donor T cells, patients with grade III or greater aGVHD of the lower GI tract, who do not respond to therapy with corticosteroids, have a dismal prognosis. Thus, efforts to improve understanding of the function of local immune and non-immune cells in regulating the inflammatory process in the GI tract during aGVHD are needed. Here, we demonstrate, using murine models of allogeneic BMT, that type 2 innate lymphoid cells (ILC2s) in the lower GI tract are sensitive to conditioning therapy and show very limited ability to repopulate from donor bone marrow. Infusion of donor ILC2s was effective in reducing the lethality of aGVHD and in treating lower GI tract disease. ILC2 infusion was associated with reduced donor proinflammatory Th1 and Th17 cells, accumulation of donor myeloid-derived suppressor cells (MDSCs) mediated by ILC2 production of IL-13, improved GI tract barrier function, and a preserved graft-versus-leukemia (GVL) response. Collectively, these findings suggest that infusion of donor ILC2s to restore gastrointestinal tract homeostasis may improve treatment of severe lower GI tract aGVHD.
急性移植物抗宿主病（aGVHD）是接受异基因干细胞移植患者最常见的并发症。尽管针对供体T细胞进行了极为积极的治疗，但患有III级或更严重下消化道aGVHD且对皮质类固醇治疗无反应的患者预后不佳。因此，需要努力增进对局部免疫细胞和非免疫细胞在aGVHD期间调节胃肠道炎症过程中功能的理解。在此，我们使用异基因骨髓移植的小鼠模型证明，下消化道中的2型固有淋巴细胞（ILC2s）对预处理疗法敏感，并且从供体骨髓中重新增殖的能力非常有限。输注供体ILC2s可有效降低aGVHD的致死率并治疗下消化道疾病。ILC2输注与供体促炎性Th1和Thl7细胞减少、由ILC2产生IL-13介导的供体髓系来源抑制细胞（MDSCs）积累、改善的胃肠道屏障功能以及保留的移植物抗白血病（GVL）反应相关。总体而言，这些发现表明输注供体ILC2s以恢复胃肠道稳态可能改善严重下消化道aGVHD的治疗。
