Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus.
Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus.
复制标题
Kindlin-3对T细胞祖细胞归巢的差异需求是非血管化和血管化胸腺的差异需求。
DOI：
10.7554/elife.35816
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发表时间：
2018-09-06
期刊：
影响因子：
7.7
通讯作者：
Moser M
中科院分区：
文献类型：
--
作者：
Moretti FA;Klapproth S;Ruppert R;Margraf A;Weber J;Pick R;Scheiermann C;Sperandio M;Fässler R;Moser M
在T细胞祖细胞在胸腺内的归巢和分化过程中，整合素介导的粘附的作用尚不明确，主要是由于功能重叠。为了规避补偿，我们在小鼠体内破坏了造血整合素调节因子kindlin-3，发现了一种进行性胸腺萎缩，主要是由T细胞祖细胞到血管化胸腺的归巢能力受损引起的。值得注意的是，妊娠中期血管系统的低剪切流动条件允许kindlin-3缺陷的胎儿肝源性T细胞祖细胞通过咽血管外渗，并定植在无血管的胸腺原基。一旦进入胸腺，kindin -3通过促进整合素依赖性与胸腺抗原提呈细胞的串音促进胸腺内T细胞增殖，而胸腺内T细胞迁移、成熟为单个阳性CD4和CD8 T细胞并释放到循环中无需kindin -3。因此，kindin -3对于整合素介导的T细胞祖细胞粘附和信号传导在低剪切力下是必不可少的，在高剪切力下是必不可少的。
The role of integrin-mediated adhesion during T cell progenitor homing to and differentiation within the thymus is ill-defined, mainly due to functional overlap. To circumvent compensation, we disrupted the hematopoietic integrin regulator kindlin-3 in mice and found a progressive thymus atrophy that is primarily caused by an impaired homing capacity of T cell progenitors to the vascularized thymus. Notably, the low shear flow conditions in the vascular system at midgestation allow kindlin-3-deficient fetal liver-derived T cell progenitors to extravasate via pharyngeal vessels and colonize the avascular thymus primordium. Once in the thymus, kindlin-3 promotes intrathymic T cell proliferation by facilitating the integrin-dependent crosstalk with thymic antigen presenting cells, while intrathymic T cell migration, maturation into single positive CD4 and CD8 T cells and release into the circulation proceed without kindlin-3. Thus, kindlin-3 is dispensable for integrin-mediated T cell progenitor adhesion and signalling at low and indispensable at high shear forces.