2. Academic Validation
  3. Dysfunction of S100A4+ effector memory CD8+ T cells aggravates asthma

Dysfunction of S100A4+ effector memory CD8+ T cells aggravates asthma

  • Eur J Immunol. 2022 Jun;52(6):978-993. doi: 10.1002/eji.202149572.
Huilei Zhang 1 2 3,  Shuangqing Liu 1 2 3,  Yanan Li 1,  Jianru Li 1 3,  Chen Ni 2,  Ming Yang 4,  Jun Dong 5,  Zhaoqing Wang 1,  Zhihai Qin 1 2 3
Affiliations

Affiliations

  • 1 Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 2 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
  • 3 University of Chinese Academy of Sciences, Beijing, China.
  • 4 Priority Research Centre for Healthy Lungs, School of Biomedical Sciences & Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia.
  • 5 German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany.
PMID: 35340022 DOI: 10.1002/eji.202149572
Abstract

Progressive loss of effector functions, especially IFN-γ secreting capability, in effector memory CD8+ T (CD8+ TEM ) cells plays a crucial role in asthma worsening. However, the mechanisms of CD8+ TEM cell dysfunction remain elusive. Here, we report that S100A4 drives CD8+ TEM cell dysfunction, impairing their protective memory response and promoting asthma worsening in an ovalbumin (OVA)-induced asthmatic murine model. We find that CD8+ TEM cells contain two subsets based on S100A4 expression. S100A4+ subsets exhibit dysfunctional effector phenotypes with increased proliferative capability, whereas S100A4- subsets retain effector function but are more inclined to Apoptosis, giving rise to a dysfunctional CD8+ TEM cell pool. Mechanistically, S100A4 upregulation of Mitochondrial Metabolism results in a decrease of acetyl-CoA levels, which impair the transcription of effector genes, especially IFN-γ, facilitating cell survival, tolerance, and memory potential. Our findings thus reveal general insights into how S100A4+ CD8+ TEM cells reprogram into dysfunctional and less protective phenotypes to aggravate asthma.

Keywords

IFN-γ; S100A4; allergic asthma; dysfunction; effector memory CD8+ T cells.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z