Back

CAR T cell targeting of inflammatory myeloid progenitors in the bone marrow remodels border-associated macrophages and reverses cognitive aging

Harris, A. S.; Rouse, J. A.; Guo, G.; Fernandez-Maestre, I.; Pal, S.; Oh, B.; Li, S.; See, W. Y.; Anderson, A.; Gewolb, J.; Soethout, M.; Habel, J.; Utama, R.; Vakoc, C. R.; Amor, C.

2026-09-28 cell biology
10.64898/2026.09.27.754777 bioRxiv
Show abstract

Aging is associated with progressive neuroinflammation and cognitive decline, yet the cellular sources that sustain this process and whether they can be targeted peripherally remain unclear. Here, we identify inflammatory border-associated macrophages (BAMs) as key drivers of neuroinflammation in aging and show that their therapeutic and prophylactic elimination through intrathecal CAR T cell therapy restores cognitive performance in mouse models of aging and Alzheimer's disease. Furthermore, targeting of aged inflammatory bone marrow myeloid progenitors through either intravenous CAR T cells, which do not infiltrate the brain, or through transplantation of CAR T-treated progenitors is sufficient to reduce neuroinflammation and cognitive impairment. These findings reveal that bone marrow myeloid progenitors harbor a heritable inflammatory transcriptional state that is transmitted to their BAM progeny, driving neuroinflammation and cognitive deterioration, and conserved in human aging. Critically, this proinflammatory state is marked by the upregulation of surface proteins, enabling precise peripheral CAR T cell targeting of these progenitors for long-lasting therapeutic effects in cognitive aging.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

1
Nature Communications
○ 5641 papers in training set
Top 15%
12.5%
Similar papers in this journal
2
Cell Reports
○ 1498 papers in training set
Top 1%
11.7%
Similar papers in this journal
3
Nature Aging
○ 60 papers in training set
Top 0.2%
8.8%
Similar papers in this journal
4
Immunity
○ 67 papers in training set
Top 0.2%
6.2%
Similar papers in this journal
5
eLife
● 5828 papers in training set
Top 26%
4.8%
Similar papers in this journal
6
Cell Metabolism
○ 57 papers in training set
Top 0.3%
4.0%
7
Cell Stem Cell
○ 62 papers in training set
Top 0.5%
3.2%
50% of probability mass above
8
The EMBO Journal
○ 309 papers in training set
Top 2%
3.2%
9
Molecular Cell
○ 350 papers in training set
Top 2%
3.2%
10
Science
● 477 papers in training set
Top 3%
3.2%
11
EMBO Reports
○ 263 papers in training set
Top 2%
2.8%
12
Cell
○ 431 papers in training set
Top 5%
2.1%
13
Science Advances
● 1243 papers in training set
Top 17%
2.1%
14
Aging Cell
○ 165 papers in training set
Top 1%
2.1%
15
Nature Metabolism
○ 69 papers in training set
Top 1.0%
2.1%
16
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 24%
2.1%
17
Nature
○ 645 papers in training set
Top 6%
2.1%
18
Nature Cell Biology
○ 118 papers in training set
Top 2%
1.7%
19
Nature Medicine
○ 125 papers in training set
Top 2%
1.5%
20
Developmental Cell
○ 196 papers in training set
Top 3%
1.5%
21
Science Translational Medicine
● 127 papers in training set
Top 2%
1.3%
22
JCI Insight
● 277 papers in training set
Top 6%
1.1%
23
Journal of Experimental Medicine
● 119 papers in training set
Top 2%
1.1%
24
Molecular Neurodegeneration
○ 55 papers in training set
Top 2%
0.8%
25
Nature Neuroscience
○ 252 papers in training set
Top 5%
0.8%
26
GeroScience
○ 109 papers in training set
Top 2%
0.6%
27
Advanced Science
○ 286 papers in training set
Top 11%
0.6%
28
Nucleic Acids Research
◐ 1281 papers in training set
Top 15%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.