# Global trends of peripheral immune tolerance research: a bibliometric and visualization analysis

**Authors:** Shixiao Kong, Chen Lin, Yuting Shen, Jun Chen

PMC · DOI: 10.3389/fimmu.2026.1730575 · Frontiers in Immunology · 2026-02-05

## TL;DR

This study maps global research trends in peripheral immune tolerance from 1989 to 2025, identifying key contributors, topics, and future directions.

## Contribution

The paper presents the first comprehensive bibliometric analysis of peripheral immune tolerance research, offering insights into its historical evolution and future trends.

## Key findings

- The annual number of publications on peripheral immune tolerance increased steadily until 2008, followed by a slight decline.
- The United States, Germany, China, and Japan were leading contributors, with Harvard University being the top institution in publications and citations.
- High-frequency keywords included autoimmunity, tolerance, and regulatory T cells, indicating key research themes.

## Abstract

Peripheral immune tolerance is a key mechanism for maintaining immune homeostasis and preventing autoimmune responses. Although numerous studies have explored its molecular and cellular basis, a comprehensive and systematic overview of the field is still lacking. This study aims to elucidate the global research landscape of peripheral immune tolerance through bibliometric analysis.

Publications related to peripheral immune tolerance from 1989 to 2025 were retrieved from the Web of Science Core Collection and Scopus databases. After removing duplicates, a total of 3,098 papers were included. CiteSpace, VOSviewer, RStudio Biblioshiny, and OriginPro were used for systematic analysis, allowing effective identification of research trends and emerging topics.

Since the 1990s, the annual number of publications on peripheral immune tolerance has steadily increased, peaking in 2008 before showing a slight decline. High-frequency keywords included autoimmunity, tolerance, and regulatory T cells. The United States, Germany, China, and Japan were the leading contributors, with Harvard University ranking first in both publication volume and citation frequency. Highly cited landmark papers by Sakaguchi, Freeman, and Curiel laid the theoretical foundation for the field. The Journal of Immunology had the highest publication count, while Nature Immunology showed the greatest impact.

This study provides the first comprehensive bibliometric analysis of global research on peripheral immune tolerance, revealing the evolution of research themes over the past three decades and forecasting future trends. The findings offer valuable data support and insights for advancing research in this field.

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## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Cd40 (CD40 antigen) [NCBI Gene 21939] {aka Bp50, GP39, HIGM1, IGM, IMD3, T-BAM}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, SLA-1 (MHC class I antigen 1) [NCBI Gene 100037293] {aka PD1, SLA-1a, sla-}, FOXP3 (forkhead box P3) [NCBI Gene 444998], RUNX1 (RUNX family transcription factor 1) [NCBI Gene 861] {aka AML1, AML1-EVI-1, AMLCR1, CBF2alpha, CBFA2, EVI-1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}
- **Diseases:** IPEX syndrome (MESH:C580192), multi-organ damage (MESH:D000092124), breast cancer (MESH:D001943), T1D (MESH:D003922), rheumatoid arthritis (MESH:D001172), CL (MESH:D002971), SLE (MESH:D008180), autoimmune disease (MESH:D001327), neurological diseases (MESH:D020271), immune-mediated diseases (MESH:C567355), cancer (MESH:D009369), colorectal, head and neck, and esophageal malignancies (MESH:D006258), vitiligo (MESH:D014820), graft-versus-host disease (MESH:D006086), inflammation (MESH:D007249), systemic autoimmune disorder (MESH:D020274)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12916357/full.md

## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916357/full.md

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Source: https://tomesphere.com/paper/PMC12916357