- Title
- Dysfunction of S100A4+ effector memory CD8+ T cells aggravates asthma
- Creator
- Zhang, Huilei; Liu, Shuangqing; Li, Yanan; Li, Jianru; Ni, Chen; Yang, Ming; Dong, Jun; Wang, Zhaoqing; Qin, Zhihai
- Relation
- European Journal of Immunology Vol. 52, Issue 6, p. 978-993
- Publisher Link
- http://dx.doi.org/10.1002/eji.202149572
- Publisher
- Wiley
- Resource Type
- journal article
- Date
- 2022
- Description
- 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.
- Subject
- S100A4; effector memory CD8+T cells; IFN-γ; dysfunction; allergic asthma
- Identifier
- http://hdl.handle.net/1959.13/1485920
- Identifier
- uon:51730
- Identifier
- ISSN:0014-2980
- Language
- eng
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