Department of Hematology, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou.
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai. China.
Cir Cir. 2023;91(5):601-614. doi: 10.24875/CIRU.22000414.
Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation.
To elucidate the role of Toll-like receptor 4 (TLR4), the major receptor for bacterial lipopolysaccharide, in the development of GVHD, we constructed a GVHD model in TLR4 knockout (TLR4) mice and monitored the cell chimerism.
In this study, we used polymerase chain reaction to identify whether TLR4 knockout (TLR4) mice were established. Before transplantation, we pretreated mice with irradiation so as to obtain an appropriate irradiation dose. Flow cytometry was applied to measure the chimerism status, the distributions of antigen-presenting cells (APCs), and T-cells in TLR4 and TLR4 recipient mice.
The general condition of TLR4 recipients was better than that of TLR4 recipients, and the TLR4 recipient mice showed less severe GVHD manifestations than the TLR4 recipient mice. Most of the APCs and T-cells in the host mouse spleen were derived from donor cells, and CD4 T-cells, including memory T-cells, were in the majority in host mice.
In general, our data show that TLR4 deletion attenuated GVHD development, which suggests that TLR4 could be used as a novel target and therapeutic paradigm in GVHD therapies.
移植物抗宿主病（GVHD）是异基因造血干细胞移植后的主要并发症。
为了阐明 Toll 样受体 4（TLR4）在 GVHD 发展中的作用，TLR4 的主要受体是细菌脂多糖，我们构建了 TLR4 敲除（TLR4）小鼠的 GVHD 模型，并监测了细胞嵌合体。
在这项研究中，我们使用聚合酶链反应来鉴定 TLR4 敲除（TLR4）小鼠是否已经建立。在移植前，我们用辐照预处理小鼠，以获得适当的辐照剂量。流式细胞术用于测量嵌合状态、抗原呈递细胞（APC）和 TLR4 和 TLR4 受体小鼠中的 T 细胞分布。
TLR4 受体的一般情况好于 TLR4 受体，TLR4 受体小鼠的 GVHD 表现比 TLR4 受体小鼠轻。宿主小鼠脾脏中的大多数 APCs 和 T 细胞来源于供体细胞，CD4 T 细胞，包括记忆 T 细胞，在宿主小鼠中占多数。
总的来说，我们的数据表明 TLR4 缺失减弱了 GVHD 的发展，这表明 TLR4 可以作为 GVHD 治疗的新靶点和治疗范例。
