Yuting Jessy Tan

All Publications

• Restored clearance of senescent neutrophils by tissue-resident macrophages limits organ aging. Science (New York, N.Y.) Tan, Y. J., Conley, T. E., Yao, F., García-Marqués, F. J., Akinyemi, D. E., Dinh, V. V., Wang, Q., Bermudez, A., Kim, J., Belk, J. A., Soehnlein, O., Pitteri, S. J., Andreasson, K. I. 2026; 393 (6808): eaea3075

  Abstract

  Aging disrupts tissue homeostasis across organ systems. Here, we identify tissue-resident macrophages (TRMs) as central coordinators of age-related organ decline through impaired clearance of senescent neutrophils, a process regulated by the immunomodulatory prostaglandin E2 (PGE2) receptor EP2. Reducing TRM EP2 signaling in aged mice preserved youthful mitochondrial fitness and prevented cognitive decline, frailty, sarcopenia, adiposity, cardiac impairment, and systemic inflammation. Plasma proteomics implicated the liver as a major source of age-associated immune change, in which reduced TRM EP2 signaling rescued neutrophil efferocytosis and prevented paracrine stress in neighboring cells. Elevated TRM EP2 expression and senescent neutrophils were also observed in aged and diseased human tissues. Pharmacologic EP2 inhibition restored youthful neutrophil clearance, establishing impaired TRM efferocytosis as a reversible driver of organ decline in aging.

  View details for DOI 10.1126/science.aea3075

  View details for PubMedID 42462036

• TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models. Nature neuroscience Wilson, E. N., Wang, C., Swarovski, M. S., Zera, K. A., Ennerfelt, H. E., Wang, Q., Chaney, A., Gauba, E., Ramos Benitez, J. A., Le Guen, Y., Minhas, P. S., Panchal, M., Tan, Y. J., Blacher, E., A Iweka, C., Cropper, H., Jain, P., Liu, Q., Mehta, S. S., Zuckerman, A. J., Xin, M., Umans, J., Huang, J., Durairaj, A. S., Serrano, G. E., Beach, T. G., Greicius, M. D., James, M. L., Buckwalter, M. S., McReynolds, M. R., Rabinowitz, J. D., Andreasson, K. I. 2024

  Abstract

  Human genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice. Trem1 deficiency rescues age-associated declines in ribose 5-phosphate. In vitro, Trem1-deficient microglia are resistant to amyloid-β42 oligomer-induced bioenergetic changes, suggesting that amyloid-β42 oligomer stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD mouse model, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy and changes in the disease-associated microglial transcriptomic signature. In aging APPSwe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake. In postmortem Alzheimer disease brain, TREM1 colocalizes with Iba1+ cells around amyloid plaques and its expression is associated with Alzheimer disease clinical and neuropathological severity. Our results suggest that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology.

  View details for DOI 10.1038/s41593-024-01610-w

  View details for PubMedID 38539014

  View details for PubMedCentralID 4369837