Third-party type 2 innate lymphoid cells prevent and treat GI tract GvHD.
Third-party type 2 innate lymphoid cells prevent and treat GI tract GvHD.
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第三方2型先天淋巴细胞预防和治疗胃肠道GvHD。
DOI：
10.1182/bloodadvances.2020001514
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发表时间：
2021-11-23
期刊：
影响因子：
7.5
通讯作者：
Serody JS
中科院分区：
文献类型：
--
作者：
Bruce DW;Kolupaev O;Laurie SJ;Bommiasamy H;Stefanski H;Blazar BR;Coghill JM;Serody JS
每周输注第三方ILC 2通过产生IL-13和双调蛋白来预防并在较小程度上治疗GVHD。ILC 2衍生的IL-13靶向宿主细胞和供体造血细胞。由供体T细胞识别宿主主要组织相容性复合物/肽多态性介导的急性移植物抗宿主病（aGVHD）仍然是异基因造血干细胞移植（allo-HSCT）的重要并发症。aGVHD最常见地涉及胃肠道、肝脏和皮肤;症状性aGVHD用皮质类固醇治疗。类固醇无反应性aGVHD是接受allo-HSCT的患者的重要问题，这些患者中<15%在诊断后存活1年。以前，我们发现输注供体先天性淋巴2型（ILC 2）细胞可以预防和治疗下胃肠道aGVHD，而对移植物抗白血病反应没有影响。这种用于临床转化的方法很麻烦，因为它需要为每个受体产生供体来源的ILC 2细胞。因此，使用第三方ILC 2细胞的能力将提供可用于治疗和/或预防aGVHD的“现成”试剂。在这里，我们发现第三方ILC 2细胞提高了allo-HSCT受者的存活率。治疗需要至少4周输注ILC 2细胞。从机制上讲，我们表明，ILC 2细胞功能完全丧失，如果细胞不能表达白细胞介素-13（IL-13）和双调蛋白。最后，我们表明，IL-13的活性具有更大的依赖于宿主而不是供体骨髓细胞上的IL-13 R的表达。产生第三方ILC 2细胞的能力为预防aGVHD提供了新的途径。
Weekly infusions of third-party ILC2s prevent, and to a lesser extent, treat GVHD via production of IL-13 and amphiregulin. ILC2-derived IL-13 targets both host cells and the donor hematopoietic cells. Acute graft-versus-host disease (aGVHD), mediated by the recognition of host major histocompatibility complex/peptide polymorphisms by donor T cells, remains a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). aGVHD most commonly involves the gastrointestinal tract, liver, and skin; symptomatic aGVHD is treated with corticosteroids. Steroid-nonresponsive aGVHD is a significant problem for patients undergoing allo-HSCT, with <15% of these patients alive 1 year after diagnosis. Previously, we found that the infusion of donor innate lymphoid type 2 (ILC2) cells could prevent and treat aGVHD of the lower gastrointestinal tract with no effect on the graft-versus-leukemia response. This approach for clinical translation is cumbersome, as it would require the generation of donor-derived ILC2 cells for each recipient. Thus, the ability to use third-party ILC2 cells would provide an “off-the-shelf” reagent that could be used to treat and/or prevent aGVHD. Here, we show that third-party ILC2 cells enhance the survival of allo-HSCT recipients. Treatment required at least 4 weekly infusions of ILC2 cells. Mechanistically, we show that ILC2 cell function was completely lost if the cells could not express both interleukin-13 (IL-13) and amphiregulin. Finally, we show that the activity of IL-13 has a greater dependence on the expression of the IL-13R on host rather than donor bone marrow cells. The ability to generate third-party ILC2 cells offers a new avenue for the prevention of aGVHD.
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影响因子：
20.3
作者：
Panoskaltsis-Mortari, A;Price, A;Blazar, BR
通讯作者：
Blazar, BR
影响因子：
20.3
作者：
Highfill, Steven L.;Rodriguez, Paulo C.;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.
影响因子：
32.4
作者：
Hanash AM;Dudakov JA;Hua G;O'Connor MH;Young LF;Singer NV;West ML;Jenq RR;Holland AM;Kappel LW;Ghosh A;Tsai JJ;Rao UK;Yim NL;Smith OM;Velardi E;Hawryluk EB;Murphy GF;Liu C;Fouser LA;Kolesnick R;Blazar BR;van den Brink MR
通讯作者：
van den Brink MR
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1200858
发表时间：
2012-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fulton LM;Carlson MJ;Coghill JM;Ott LE;West ML;Panoskaltsis-Mortari A;Littman DR;Blazar BR;Serody JS
通讯作者：
Serody JS