| First Author | Zhang H | Year | 2022 |
| Journal | Eur J Immunol | Volume | 52 |
| Issue | 6 | Pages | 978-993 |
| PubMed ID | 35340022 | Mgi Jnum | J:326840 |
| Mgi Id | MGI:7311836 | Doi | 10.1002/eji.202149572 |
| Citation | Zhang H, et al. (2022) Dysfunction of S100A4(+) effector memory CD8(+) T cells aggravates asthma. Eur J Immunol 52(6):978-993 |
| abstractText | Progressive loss of effector functions, especially IFN-gamma 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-gamma, 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. |
