Biotechnology Institute Thurgau (BITg) at the University of Konstanz, CH-8280, Kreuzlingen, Switzerland.
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Sydney, Australia.
BMC Biol. 2022 Aug 24;20(1):189. doi: 10.1186/s12915-022-01386-0.
T cell activation leads to increased expression of the receptor for the iron transporter transferrin (TfR) to provide iron required for the cell differentiation and clonal expansion that takes place during the days after encounter with a cognate antigen. However, T cells mobilise TfR to their surface within minutes after activation, although the reason and mechanism driving this process remain unclear.
Here we show that T cells transiently increase endocytic uptake and recycling of TfR upon activation, thereby boosting their capacity to import iron. We demonstrate that increased TfR recycling is powered by a fast endocytic sorting pathway relying on the membrane proteins flotillins, Rab5- and Rab11a-positive endosomes. Our data further reveal that iron import is required for a non-canonical signalling pathway involving the kinases Zap70 and PAK, which controls adhesion of the integrin LFA-1 and eventually leads to conjugation with antigen-presenting cells.
Altogether, our data suggest that T cells boost their iron importing capacity immediately upon activation to promote adhesion to antigen-presenting cells.
T 细胞激活会导致铁转运蛋白转铁蛋白（TfR）受体的表达增加，为与同源抗原相遇后的细胞分化和克隆扩增提供所需的铁。然而，T 细胞在激活后几分钟内就会将 TfR 募集到其表面，尽管驱动这一过程的原因和机制仍不清楚。
在这里，我们表明 T 细胞在激活后会短暂增加 TfR 的内吞作用和循环回收，从而提高其摄取铁的能力。我们证明，TfR 循环的增加是由一个快速的内吞分拣途径提供动力的，该途径依赖于 flotillins 等膜蛋白、Rab5 和 Rab11a 阳性内体。我们的数据还进一步表明，铁的摄取对于涉及激酶 Zap70 和 PAK 的非经典信号通路是必需的，该通路控制着整合素 LFA-1 的黏附，最终导致与抗原呈递细胞的共轭。
总之，我们的数据表明，T 细胞在激活后立即增强其摄取铁的能力，以促进与抗原呈递细胞的黏附。
