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; Chih-Wei Hu; Jui-Yu Chang; Shuoh-Wen Chen; Ting-An Lin; Eric Chang-Yi Lin; Min-Hui Chen; Chuen-Mi Yang; Hsuan-Ying Lu; Ching-Jung Teng; Yuan-I Chang

doi:10.1111/acel.70154

Impaired Cytokine Secretion Contributes to Age-Dependent Immune Dysfunction in SARS Coronavirus Response and Is Restored by Young CD11b-Positive Cell Transfer

Aging Cell. 2025 Jun 29:e70154. doi: 10.1111/acel.70154. Online ahead of print.

Authors

Yu-Xuan Wu¹, Chih-Wei Hu², Jui-Yu Chang³, Shuoh-Wen Chen¹, Ting-An Lin^{1

4

5}, Eric Chang-Yi Lin^{1

6}, Min-Hui Chen¹, Chuen-Mi Yang², Hsuan-Ying Lu², Ching-Jung Teng⁷, Yuan-I Chang¹

Affiliations

¹ Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
² Experimental Animal Center, Institute of Preventive Medicine, National Defense Medical College, New Taipei City, Taiwan.
³ Department of Biotechnology and Laboratory Science in Medicine, College of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
⁴ Department of Internal Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
⁵ Division of Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan.
⁶ Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁷ School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan.

PMID: 40583123
DOI: 10.1111/acel.70154

Abstract

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⁺ cells. Notably, the adoptive transfer of young CD11b⁺ 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.

Abstract

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