TIA1 is required for microglial activation in tauopathy
Abstract
The RNA-binding protein T cell intracellular antigen-1 (TIA1) regulates cellular stress responses and tau pathology, key contributors to the pathophysiology of tauopathies, including Alzheimer’s disease (AD). TIA1 acts in peripheral monocytes to inhibit inflammation, but its function in central microglia, critical to neuroinflammation and disease progression, remains unknown. Here, we crossed TIA1 microglial conditional knockout (cKO) mice (using a Cx3cr1 -driven Cre element) with the PS19 P301S MAPT mouse model of tauopathy and demonstrated that TIA1 promotes microglial activation, with a corresponding suppression of microglia activation upon TIA1cKO. We observe striking reductions in cytokine ( Tnf-α and Il-1β ) and sensome markers ( Clec7a , Trem2 , and Itgax ); importantly, these reductions were accompanied by decreases in tau pathology. Proteomic analyses show TIA1 interaction with the microglial proteins C1Q, previously implicated in microglial activation. These results position TIA1 as a regulator of neuroinflammation and tauopathy in CX3CR1-expressing myeloid cells, including microglia, with potentially divergent functions in central versus peripheral immune compartments.
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BibTeX
@article{webber2026tia1,
title = {{TIA1 is required for microglial activation in tauopathy}},
author = {Chelsea J. Webber and Sophie J.F. van der Spek and Anna Lourdes Cruz and Sambhavi Puri and Yiren Shao and Cheng Zhang and Jacqueline T.M. Aw and Georgia-Zeta Papadimitriou and Rebecca Roberts and Kiki Jiang and Thuc Nhan Tran and Lushuang Zhang and Alexandria Taylor and Zihan Wang and Katarnut Tobunluepop and Madhav Ellini and Jacob Porter and Ionnis Sotiropoulos and Andrew Emili and Joana Silva and Hu Li and Benjamin Wolozin},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2026.118199},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124726012787},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - TIA1 is required for microglial activation in tauopathy
AU - Chelsea J. Webber
AU - Sophie J.F. van der Spek
AU - Anna Lourdes Cruz
AU - Sambhavi Puri
AU - Yiren Shao
AU - Cheng Zhang
AU - Jacqueline T.M. Aw
AU - Georgia-Zeta Papadimitriou
AU - Rebecca Roberts
AU - Kiki Jiang
AU - Thuc Nhan Tran
AU - Lushuang Zhang
AU - Alexandria Taylor
AU - Zihan Wang
AU - Katarnut Tobunluepop
AU - Madhav Ellini
AU - Jacob Porter
AU - Ionnis Sotiropoulos
AU - Andrew Emili
AU - Joana Silva
AU - Hu Li
AU - Benjamin Wolozin
PY - 2026
DA - 2026/10/30
JO - Cell Reports
DO - 10.1016/j.celrep.2026.118199
UR - https://linkinghub.elsevier.com/retrieve/pii/S2211124726012787
AB - The RNA-binding protein T cell intracellular antigen-1 (TIA1) regulates cellular stress responses and tau pathology, key contributors to the pathophysiology of tauopathies, including Alzheimer’s disease (AD). TIA1 acts in peripheral monocytes to inhibit inflammation, but its function in central microglia, critical to neuroinflammation and disease progression, remains unknown. Here, we crossed TIA1 microglial conditional knockout (cKO) mice (using a Cx3cr1 -driven Cre element) with the PS19 P301S MAPT mouse model of tauopathy and demonstrated that TIA1 promotes microglial activation, with a corresponding suppression of microglia activation upon TIA1cKO. We observe striking reductions in cytokine ( Tnf-α and Il-1β ) and sensome markers ( Clec7a , Trem2 , and Itgax ); importantly, these reductions were accompanied by decreases in tau pathology. Proteomic analyses show TIA1 interaction with the microglial proteins C1Q, previously implicated in microglial activation. These results position TIA1 as a regulator of neuroinflammation and tauopathy in CX3CR1-expressing myeloid cells, including microglia, with potentially divergent functions in central versus peripheral immune compartments.
SN - 2211-1247
ER -