Arp2/3 complex controls T cell homeostasis by maintaining surface TCR levels via regulating TCR+ endosome trafficking

Ye Zhang,Haiyun Feng,Xiaolong Liu,Haifeng Liu,Xiaoyan Zhu,Yan Liu,Hao Shen

doi:10.1038/s41598-017-08357-4

Abstract

T cell receptor (TCR) signaling is important for T cell homeostasis and function. However, how surface TCR levels are regulated and its biological significance on T cells remains largely unknown. Here, we show that the T cell-specific deletion of Arpc2, a component of Arp2/3 complex, results in compromised peripheral T cell homeostasis. Arp2/3 complex-nucleated actin filaments are essential for maintaining surface TCR levels by regulating TCR+ endosome trafficking in resting state and controlling polarization of TCR+ endosomes during immune synapse formation in T cells. Additionally, Arpc2-TKO T cells are unable to form immune synapse. Interestingly, defected T cell homeostasis is caused by reduced surface TCR levels but not impaired immune synapse formation. Collectively, our findings suggest that Arp2/3 complex-nucleated actin filaments are required for maintaining surface TCR levels via regulating TCR+ endosome trafficking which is essential for T cell homeostasis.

Highlights

Peripheral T cells are maintained at a constant cell number so that they can efficiently recognize foreign antigens and protect the host from pathogen invasion
T cell homeostasis is essential for the functions of the adaptive immune system because it maintains a constant pool of peripheral T cells
This process is regulated by homeostatic signals that are initiated following the recognition of the self-peptide-major histocompatiblity complex (MHC) complex and IL-7 signals[1]

Summary

Introduction

Peripheral T cells are maintained at a constant cell number so that they can efficiently recognize foreign antigens and protect the host from pathogen invasion. T cell homeostasis requires the combined regulation of T cell survival and proliferation, which are mediated by complex homeostatic signals[1,2,3]. TCR is required for homeostatic signals, the mechanisms that maintain surface TCR levels and its biological effects on T cell homeostasis remain largely unknown. The impaired surface TCR maintenance was caused by defective TCR+ endosome trafficking, which is promoted by Arp2/3 complex-nucleated actin filaments and such compromised actin filaments were accounted for defective polarization of TCR+ endosome during immune synapse formation. Our data demonstrate that the defective homeostasis observed in Arpc2-TKO T cells is caused by a reduction in surface TCR levels but not impaired immune synapse formation. Our research supports an essential role for the Arp2/3 complex in surface TCR maintenance and such TCR levels are critical for T cell homeostasis

Methods

Results

Conclusion