Evidence map›Paper›PMID 39949060›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Modulating the PD-1-FABP5 axis in ILC2s to regulate adipose tissue metabolism in obesity.

Jongho Ham, Jaemoon Koh, Jungeun Kim, Joo-Youn Cho, TaeSoo Kim, Doo Hyun Chung, Yong-Soo Bae, Hye Young Kim

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

8 authors.

Jongho HamLaboratory of Mucosal Immunology, Department of Biomedical and Sciences BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul 03080, South Korea; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, South Korea; CIRNO, Sungkyunkwan University, Suwon 16419, South Korea.
Jaemoon KohDepartment of Pathology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
Jungeun KimDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
Joo-Youn ChoDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Kidney Research Institute, Seoul National University Medical Research Center, Seoul 03080, South Korea.
TaeSoo KimDepartment of Life Science, Multitasking Macrophage Research Center, Ewha Womans University, Seoul 03760, South Korea.
Doo Hyun ChungDepartment of Pathology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
Yong-Soo BaeDepartment of Biological Sciences, Sungkyunkwan University, Suwon 16419, South Korea; CIRNO, Sungkyunkwan University, Suwon 16419, South Korea.
Hye Young KimLaboratory of Mucosal Immunology, Department of Biomedical and Sciences BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul 03080, South Korea; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, South Korea; Department of Life Science, Multitasking Macrophage Research Center, Ewha Womans University, Seoul 03760, South Korea; CIRNO, Sungkyunkwan University, Suwon 16419, South Korea. Electronic address: hykim11@snu.ac.kr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Obesity is closely linked to metabolic dysregulation and chronic inflammation, which significantly impact immune cell functions in adipose tissue. Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of energy homeostasis, positioning them as promising targets for obesity management. However, the mechanisms governing ILC2 activity and their therapeutic potential in obesity are not fully understood. In this study, we demonstrate that ILC2s in obese adipose tissue exhibit increased PD-1 expression, leading to an exhausted phenotype with diminished cytokine production and proliferation. Elevated osteopontin (OPN) levels in adipose tissue are associated with higher PD-1 expression on ILC2s, while adipocyte-derived PD-L1 interacts with PD-1 to further impair ILC2 functionality. Importantly, blocking PD-1 signaling prevents weight gain and alleviates obesity-related metabolic dysfunctions. In addition, the adoptive transfer of PD-1-deficient ILC2s reduces diabetic phenotypes in obese models. Mechanistically, PD-1 signaling drives metabolic reprogramming in ILC2s, affecting fatty acid uptake and energy metabolism through the downregulation of fatty acid binding protein 5 (FABP5). These results, corroborated by findings in human adipose tissue, suggest a conserved OPN-PD-1 axis. Our study identifies the OPN-PD-1-FABP5 pathway as a crucial regulator of ILC2 function in adipose tissue and presents an emerging immune cell-based therapeutic target for obesity treatment.

Indexed as

Adipose TissueFatty Acid-Binding ProteinsImmunity, InnateLymphocytesObesityProgrammed Cell Death 1 ReceptorAnimalsDisease Models, AnimalEnergy MetabolismHumansMaleMiceMice, Inbred C57BLOsteopontinSignal TransductionFABP5 protein, humanFatty Acid-Binding ProteinsOsteopontinProgrammed Cell Death 1 ReceptorFABP5fatty acid metabolismimmune exhaustionimmunometabolisminnate lymphoid cellmetabolic dysregulationobesityosteopontinPD-1

Identifiers

PMID39949060
PMCPMC11997476

What Socratic holds

Textmetadata
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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 Socratic graph.