Dysfunction of S100A4+ effector memory CD8+ T cells aggravates asthma.
Eur J Immunol
; 52(6): 978-993, 2022 06.
Article
en En
| MEDLINE
| ID: mdl-35340022
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Asma
/
Linfocitos T CD8-positivos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China