Evidence map›Paper›PMID 35717259›Full record

ArticleMolecular neurodegeneration2022

LILRB2-mediated TREM2 signaling inhibition suppresses microglia functions.

Peng Zhao, Yuanzhong Xu, Lu-Lin Jiang, Xuejun Fan, Zhiqiang Ku, Leike Li, Xiaoye Liu, Mi Deng, Hisashi Arase, Jay-Jiguang Zhu and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. The role of DAP12 in immune-related inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  6. Article
  7. Review
  8. Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026
    Review
  9. Analyses of plasma multi-omic data across ancestries identify novel pathways implicated in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Trem2 negatively regulates the MTOR-PKCα axis to protect againstFrontiers in cellular and infection microbiology · 2026
    Article
  15. Review
  16. Review
  17. Review
  18. Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 3 countries.

Peng ZhaoTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Yuanzhong XuCenter for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Lu-Lin JiangNeuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Xuejun FanTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Zhiqiang KuTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Leike LiTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Xiaoye LiuDepartment of Physiology, UT Southwestern Medical Center, Dallas, TX, USA.
Mi DengDepartment of Physiology, UT Southwestern Medical Center, Dallas, TX, USA.
Hisashi AraseDepartment of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Jay-Jiguang ZhuDepartment of Neurosurgery, University of Texas Health Science Center in Houston, McGovern Medical School and Memorial Hermann, Houston, TX, USA.
Timothy Y HuangNeuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Yingjun ZhaoState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Chengcheng ZhangDepartment of Physiology, UT Southwestern Medical Center, Dallas, TX, USA.
Huaxi XuState Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Qingchun TongCenter for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Ningyan ZhangTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA. ningyan.zhang@uth.tmc.edu.
Zhiqiang AnTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA. zhiqiang.an@uth.tmc.edu.ORCID 0000-0001-9309-2335
Brown Foundation · USSouthwestern Medical Center · USSanford Burnham Prebys Medical Discovery Institute · USXiamen University · CNMemorial Hermann · USThe University of Osaka · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMicroglia plays crucial roles in Alzheimer's disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs.

methodsTo specifically interrogate LILRB2-ligand (oAβ and PS) interactions and microglia functions, we generated potent antagonistic LILRB2 antibodies with sub-nanomolar level activities. The biological effects of LILRB2 antagonist antibody (Ab29) were studied in human induced pluripotent stem cell (iPSC)-derived microglia (hMGLs) for migration, oAβ phagocytosis, and upregulation of inflammatory cytokines. Effects of the LILRB2 antagonist antibody on microglial responses to amyloid plaques were further studied in vivo using stereotaxic grafted microglia in 5XFAD mice.

resultsWe confirmed the expression of both LILRB2 and TREM2 in human brain microglia using immunofluorescence. Upon co-ligation of the LILRB2 and TREM2 by shared ligands oAβ or PS, TREM2 signaling was significantly inhibited. We identified a monoclonal antibody (Ab29) that blocks LILRB2/ligand interactions and prevents TREM2 signaling inhibition mediated by LILRB2. Further, Ab29 enhanced microglia phagocytosis, TREM2 signaling, migration, and cytokine responses to the oAβ-lipoprotein complex in hMGL and microglia cell line HMC3. In vivo studies showed significantly enhanced clustering of microglia around plaques with a prominent increase in microglial amyloid plaque phagocytosis when 5XFAD mice were treated with Ab29.

conclusionsThis study revealed for the first time the molecular mechanisms of LILRB2-mediated inhibition of TREM2 signaling in microglia and demonstrated a novel approach of enhancing TREM2-mediated microglia functions by blocking LILRB2-ligand interactions. Translationally, a LILRB2 antagonist antibody completely rescued the inhibition of TREM2 signaling by LILRB2, suggesting a novel therapeutic strategy for improving microglial functions.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsAnimalsBrainHumansLigandsMembrane GlycoproteinsMiceMicrogliaPlaque, AmyloidReceptors, ImmunologicLigandsLILRB2 protein, humanMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanTrem2 protein, mouse5XFAD miceAlzheimer’s diseaseAmyloidAntibodyITAMITIMLILRB2MicrogliaPhagocytosisTREM2

Identifiers

PMID35717259
PMCPMC9206387
OpenAlexW4283069055

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.