tetano
Editor, Senior Moderator
Aging Cell
. 2025 Jun 29:e70154.
doi: 10.1111/acel.70154. Online ahead of print. Impaired Cytokine Secretion Contributes to Age-Dependent Immune Dysfunction in SARS Coronavirus Response and Is Restored by Young CD11b-Positive Cell Transfer
Yu-Xuan Wu[SUP] 1 [/SUP], Chih-Wei Hu[SUP] 2 [/SUP], Jui-Yu Chang[SUP] 3 [/SUP], Shuoh-Wen Chen[SUP] 1 [/SUP], Ting-An Lin[SUP] 1 4 5 [/SUP], Eric Chang-Yi Lin[SUP] 1 6 [/SUP], Min-Hui Chen[SUP] 1 [/SUP], Chuen-Mi Yang[SUP] 2 [/SUP], Hsuan-Ying Lu[SUP] 2 [/SUP], Ching-Jung Teng[SUP] 7 [/SUP], Yuan-I Chang[SUP] 1 [/SUP]
Affiliations
COVID-19 mortality disproportionately affects the elderly, yet the cellular and molecular factors contributing to age-related immune system remodeling remain unclear. Using SARS-CoV-derived ssRNA sequences, we modeled age-dependent immune responses in mice. Aged mice exhibited higher mortality and severe lung inflammation upon viral ssRNA challenge, mirroring clinical observations. We uncovered a pre-existing inflammatory state in aged mice, characterized by elevated baseline levels of specific immune cells and cytokines correlating with poor outcomes. Age-related immune dysfunction stemmed from impaired IRF7 signaling and defective SNARE-mediated cytokine secretion in CD11b[SUP]+[/SUP] cells. Notably, the adoptive transfer of young CD11b[SUP]+[/SUP] cells to aged mice exposed to SARS-CoV2 ssRNA reduced mortality, alleviated lung inflammation, and normalized cytokine profiles. These findings provide insights into age-related immune dysregulation during viral challenges and suggest potential therapeutic strategies for severe COVID-19 in the elderly.
Keywords: IRF7; SARS‐CoV; SNARE; aging; innate immunity.
. 2025 Jun 29:e70154.
doi: 10.1111/acel.70154. Online ahead of print. Impaired Cytokine Secretion Contributes to Age-Dependent Immune Dysfunction in SARS Coronavirus Response and Is Restored by Young CD11b-Positive Cell Transfer
Yu-Xuan Wu[SUP] 1 [/SUP], Chih-Wei Hu[SUP] 2 [/SUP], Jui-Yu Chang[SUP] 3 [/SUP], Shuoh-Wen Chen[SUP] 1 [/SUP], Ting-An Lin[SUP] 1 4 5 [/SUP], Eric Chang-Yi Lin[SUP] 1 6 [/SUP], Min-Hui Chen[SUP] 1 [/SUP], Chuen-Mi Yang[SUP] 2 [/SUP], Hsuan-Ying Lu[SUP] 2 [/SUP], Ching-Jung Teng[SUP] 7 [/SUP], Yuan-I Chang[SUP] 1 [/SUP]
Affiliations
- PMID: 40583123
- DOI: 10.1111/acel.70154
COVID-19 mortality disproportionately affects the elderly, yet the cellular and molecular factors contributing to age-related immune system remodeling remain unclear. Using SARS-CoV-derived ssRNA sequences, we modeled age-dependent immune responses in mice. Aged mice exhibited higher mortality and severe lung inflammation upon viral ssRNA challenge, mirroring clinical observations. We uncovered a pre-existing inflammatory state in aged mice, characterized by elevated baseline levels of specific immune cells and cytokines correlating with poor outcomes. Age-related immune dysfunction stemmed from impaired IRF7 signaling and defective SNARE-mediated cytokine secretion in CD11b[SUP]+[/SUP] cells. Notably, the adoptive transfer of young CD11b[SUP]+[/SUP] cells to aged mice exposed to SARS-CoV2 ssRNA reduced mortality, alleviated lung inflammation, and normalized cytokine profiles. These findings provide insights into age-related immune dysregulation during viral challenges and suggest potential therapeutic strategies for severe COVID-19 in the elderly.
Keywords: IRF7; SARS‐CoV; SNARE; aging; innate immunity.