The Confluence of Autoinflammation, Autoimmunity, and Peripheral Immune Tolerance: A New Chapter in Immunological Harmony
Abstract
Abstract
The 2025 Nobel Prize in Physiology or Medicine celebrated the discovery of mechanisms of peripheral immune tolerance, completing the immunological spectrum that spans autoinflammation and autoimmunity. This editorial contextualizes the award within decades of research illustrating how regulatory T cells (Tregs) and other tolerance mechanisms uphold self-integrity while sustaining host defense. Recent discoveries regarding transcriptional regulation, T-cell plasticity, and tumor immunology underscore the importance of immune balance in both health and disease.
Keywords
Peripheral immune tolerance Regulatory T cell Autoimmunity Immune homeostasis Foxp3–Ikzf1 axis
References
- 1. Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K, Ohkura N. Regulatory T Cells and Human Disease. Annu Rev Immunol. 2020 Apr 26;38:541-566. doi: 10.1146/annurev-immunol-042718-041717. Epub 2020 Feb 4. PMID: 32017635.
- 2. Zeng H, Zhang R, Jin B, Chen L. Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance. Cell Mol Immunol. 2015 Sep;12(5):566-71. doi: 10.1038/cmi.2015.44. Epub 2015 Jun 8. PMID: 26051475; PMCID: PMC4579656.
- 3. Ichiyama K, Long J, Kobayashi Y, Horita Y, Kinoshita T, Nakamura Y, Kominami C, Georgopoulos K, Sakaguchi S. Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity. Immunity. 2024 Sep 10;57(9):2043-2060.e10. doi: 10.1016/j.immuni.2024.07.010. Epub 2024 Aug 6. PMID: 39111316.
- 4. Tay C, Tanaka A, Sakaguchi S. Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy. Cancer Cell. 2023 Mar 13;41(3):450-465. doi: 10.1016/j.ccell.2023.02.014. PMID: 36917950.
- 5. Kuratani A, Okamoto M, Kishida K, Okuzaki D, Sasai M, Sakaguchi S, Arase H, Yamamoto M. Platelet factor 4-induced TH1-Treg polarization suppresses antitumor immunity. Science. 2024 Nov 22;386(6724):eadn8608. doi: 10.1126/science.adn8608. Epub 2024 Nov 22. PMID: 39571033.
Otoinflamasyon, Otoimmünite ve Periferal İmmün Toleransın Keşismesi: İmmünolojik Ahenkte Yeni Bir Bölüm
Abstract
Öz
Fizyoloji veya tıp alanında 2025 Nobel ödülü otoinflamasyon ve otoimmüniteyi kapsayan immünolojik spektrumu tamamlayan periferal immün tolerans mekanizmalarının keşfini kutladı. Bu editöryal on yıllarca süren bir çalışmanın ödülü olan bu araştırmada regülatör T hücreler (Treg) ve öteki immün tolerans mekanizmalarının konak savunması devam ederken öz bütünlüğünün nasıl olduğunu ele almaktadır. Transkripsiyonel regülasyon, T hücre plastisise ve tümör imünolojisini ilgilendiren son çalışmalar sağlıkta ve hastalıkta immün dengenin öneminin altını çizmektedir.
References
- 1. Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K, Ohkura N. Regulatory T Cells and Human Disease. Annu Rev Immunol. 2020 Apr 26;38:541-566. doi: 10.1146/annurev-immunol-042718-041717. Epub 2020 Feb 4. PMID: 32017635.
- 2. Zeng H, Zhang R, Jin B, Chen L. Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance. Cell Mol Immunol. 2015 Sep;12(5):566-71. doi: 10.1038/cmi.2015.44. Epub 2015 Jun 8. PMID: 26051475; PMCID: PMC4579656.
- 3. Ichiyama K, Long J, Kobayashi Y, Horita Y, Kinoshita T, Nakamura Y, Kominami C, Georgopoulos K, Sakaguchi S. Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity. Immunity. 2024 Sep 10;57(9):2043-2060.e10. doi: 10.1016/j.immuni.2024.07.010. Epub 2024 Aug 6. PMID: 39111316.
- 4. Tay C, Tanaka A, Sakaguchi S. Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy. Cancer Cell. 2023 Mar 13;41(3):450-465. doi: 10.1016/j.ccell.2023.02.014. PMID: 36917950.
- 5. Kuratani A, Okamoto M, Kishida K, Okuzaki D, Sasai M, Sakaguchi S, Arase H, Yamamoto M. Platelet factor 4-induced TH1-Treg polarization suppresses antitumor immunity. Science. 2024 Nov 22;386(6724):eadn8608. doi: 10.1126/science.adn8608. Epub 2024 Nov 22. PMID: 39571033.
Details
| Primary Language | English |
|---|---|
| Subjects | Medical Education |
| Journal Section | Editorial |
| Authors | |
| Submission Date | December 3, 2025 |
| Acceptance Date | December 19, 2025 |
| Publication Date | December 31, 2025 |
| Published in Issue | Year 2025 Volume: 47 Issue: 4 |