Controlling the burn and fueling the fire: defining the role for the alarmin interleukin-33 in alloimmunity.
Controlling the burn and fueling the fire: defining the role for the alarmin interleukin-33 in alloimmunity.
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DOI：
10.1097/mot.0000000000000265
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发表时间：
2016-02
影响因子：
2.2
通讯作者：
Turnquist HR
中科院分区：
文献类型：
--
作者：
Liu Q;Turnquist HR
提供IL-33和IL-33靶向免疫细胞免疫生物学最新进展的一般更新。我们还讨论了IL-33在改变介导宿主抗移植物和移植物抗宿主同种异体反应的同种免疫反应中的潜在作用。基质细胞和白细胞显示IL-33的调节表达，并且可以主动或被动地分泌这种多效性细胞因子。ILC 2和大部分组织驻留Treg表达膜结合的ST 2，即IL-33受体。虽然Treg被认为是免疫细胞的炎症功能的抑制因子，但ILC 2和组织驻留Treg都可以在组织修复和稳态中发挥关键作用。IL-33在移植中的作用尚不清楚。然而，与其他疾病模型一样，IL-33在同种免疫中的功能似乎是相当多效性的。IL-33与心脏移植环境中的免疫调节和移植物保护相关。然而，它是高度促炎性的，并通过其刺激1型免疫的能力刺激致命的移植物抗宿主病（GVHD）。对实体器官和细胞移植中IL-33/ST 2信号通路和ST 2+细胞群体的深入研究是必要的。更好地了解这一重要途径将提供有前途的治疗靶点，控制致病性同种异体免疫反应，以及可能促进移植后调节和修复免疫细胞的功能。
To provide a general update on recent developments in the immunobiology of IL-33 and IL-33-targeted immune cells. We also discuss emerging concepts regarding the potential role IL-33 appears to play in altering alloimmune responses mediating host-versus-graft and graft-versus-host alloresponses. Stromal cells and leukocytes display regulated expression of IL-33 and may actively or passively secrete this pleotropic cytokine. ILC2 and a large proportion of tissue resident Treg express membrane-bound ST2, the IL-33 receptor. While Treg are appreciated suppressors of the inflammatory function of immune cells, both ILC2s and tissue resident Treg could play key roles in tissue repair and homeostasis. The functions of IL-33 in transplantation are poorly understood. However, like other disease models, the functions of IL-33 in alloimmunity appear to be quite pleiotropic. IL-33 is associated with immune regulation and graft protection in cardiac transplant settings. Yet, it is highly pro-inflammatory and stimulates lethal graft-versus-host disease (GVHD) through its capacity to stimulate Type 1 immunity. Intensive studies on IL-33/ST2 signaling pathways and ST2+ cell populations in solid organ and cell transplantation are warranted. A better understanding of this important pathway will provide promising therapeutic targets controlling pathogenic alloimmune responses, as well as potentially facilitating the function of regulatory and reparative immune cells post-transplantation.