Altered follicular helper T cell impaired antibody production in a murine model of myelodysplastic syndromes.
Altered follicular helper T cell impaired antibody production in a murine model of myelodysplastic syndromes.
复制标题
改变滤泡辅助 T 细胞会损害骨髓增生异常综合征小鼠模型中的抗体产生。
DOI：
10.18632/oncotarget.21548
复制
发表时间：
2017-11-17
期刊：
影响因子：
--
通讯作者：
Shao Z
中科院分区：
文献类型：
--
作者：
Jiang H;Cui N;Yang L;Liu C;Yue L;Guo L;Wang H;Shao Z
骨髓增生异常综合征（MDS）是一组克隆性造血系统疾病，具有进展为急性髓系白血病的高风险。MDS患者存在免疫缺陷，包括T和B细胞功能障碍。滤泡辅助性T细胞（Tfh，CD 4 + CXCR 5+）是辅助性T细胞的重要亚群，参与生殖中心的形成和B细胞的分化。本研究利用NUP 98-HOXD 13转基因小鼠（NHD 13）建立MDS模型，研究Tfh在MDS中的比例和功能。流式细胞术检测NHD 13小鼠骨髓和脾脏中Tfh的比例较野生型（WT）小鼠降低。免疫组化显示NHD 13小鼠脾脏CXCR 5+细胞减少，PD-1+细胞增加。NHD 13小鼠Tfh上表达的活性标志物（ICOS、CD 40 L和OX 40）减少。相比之下，NHD 13小鼠Tfh上的PD-1表达高于WT小鼠。与NHD 13小鼠Tfh共培养后，B细胞IgG和IgM的产生减少。总之，Tfh在MDS小鼠模型中的比例和功能发生了改变。Tfh功能障碍和减少可能会抑制B细胞分化和抗体产生。Tfh异常可能与MDS的免疫耐受有关，促进MDS的进展。
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic diseases which have a high risk of progressing to acute myeloid leukemia. MDS patients have immunologic deficiency, including T and B cells dysfunction. Follicular T helper cells (Tfh, CD4+CXCR5+) are an important subset of helper T cells which help to the formation of germinal centers and B cells differentiation. In this study, we investigated the proportion and function of Tfh using NUP98-HOXD13 transgenic (NHD13) mice model with MDS phenotype. The proportion of Tfh from bone marrow and spleen of NHD13 mice decreased compared with wild type (WT) mice tested by flow cytometry. In NHD13 mice spleens, there were decreased CXCR5+ cells and increased PD-1+ cells using immunohistochemistry. The active markers (ICOS, CD40L and OX40) expressed on Tfh of NHD13 mice were decreased. In contrast, PD-1 expression on Tfh of NHD13 mice was higher than that of WT mice. After coculture with Tfh from NHD13 mice, IgG and IgM production of B cells were decreased. In conclusion, the proportion and function of Tfh in the MDS mice model were altered. The dysfunction and reduction of Tfh may inhibit B cells differentiation and antibody production. Abnormal Tfh might contribute to the immune tolerance promoting the progression of MDS.
登录
查看更多内容
影响因子：
11.4
作者：
Cheng G;Liu F;Asai T;Lai F;Man N;Xu H;Chen S;Greenblatt S;Hamard PJ;Ando K;Chen X;Wang L;Martinez C;Tadi M;Wang L;Xu M;Yang FC;Shiekhattar R;Nimer SD
通讯作者：
Nimer SD
影响因子：
158.5
作者：
Tehranchi, Ramin;Woll, Petter S.;Jacobsen, Sten Eirik W.
通讯作者：
Jacobsen, Sten Eirik W.
影响因子：
20.3
作者：
Slape, Christopher;Liu, Leah Y.;Aplan, Peter D.
通讯作者：
Aplan, Peter D.
影响因子：
11.4
作者：
Gañán-Gómez I;Wei Y;Starczynowski DT;Colla S;Yang H;Cabrero-Calvo M;Bohannan ZS;Verma A;Steidl U;Garcia-Manero G
通讯作者：
Garcia-Manero G
影响因子：
12.4
作者：
Guirguis, A. A.;Slape, C. I.;Curtis, D. J.
通讯作者：
Curtis, D. J.