ER stress and its PERK branch enhance TCR-induced activation in regulatory T cells
| Autor: | Yong-ming Yao, Tao Ma, Jian-Nan Hu, Ning Luo, Ying Liu, Zhen-Zhen Feng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Receptors Antigen T-Cell Biophysics chemical and pharmacologic phenomena Activating Transcription Factor 4 T-Lymphocytes Regulatory Biochemistry Mice eIF-2 Kinase 03 medical and health sciences 0302 clinical medicine Animals Endoplasmic Reticulum Chaperone BiP Molecular Biology Transcription factor Mice Inbred BALB C Chemistry Endoplasmic reticulum T-cell receptor ATF4 FOXP3 hemic and immune systems Cell Biology Endoplasmic Reticulum Stress Protein kinase R Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Unfolded Protein Response Unfolded protein response Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 563:8-14 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.05.061 |
| Popis: | Although accumulating evidence indicates participation of endoplasmic reticulum (ER) stress pathway or the unfolded protein response (UPR) in immunity, there still exists little information linking ER stress to regulatory T cells (Tregs). To evaluate the potential contribution of the UPR, we tested the effects of thapsigargin (TG), an ER stress inducer, on the function of Tregs. Here we reported that TG stimulation induced the up-regulation of the endoplasmic reticulum (ER)-stress chaperon Glucose-Regulated Protein 78 (GRP78), which is a master regulator of the UPR, the phosphorylation of eukaryotic initiation factor 2 alpha (elF2α) and the induction of activating transcription factor 4 (ATF4), which are both protein kinase R (PKR)-like ER kinase (PERK) downstream targets in Tregs. Simultaneously, we demonstrated that, under ER stress conditions, Tregs presented enhanced functional activity upon TCR stimulation, as illustrated with forkhead box transcription factor (Foxp3) expression, interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production and suppressive functional analysis. Notably, pretreatment with GSK2656157, a potent and selective PERK inhibitor, markedly diminished the TG-induced hyperresponsiveness of Tregs upon T cell antigen receptor (TCR) stimulation. Therefore, our findings illustrated the inter-connection and coordination of the evolutionarily conserved ER stress response and TCR signaling in Tregs and uncover a critical new role of the PERK branch of UPR in the regulation of Tregs function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect