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Immune Regulatory Mechanisms in the Pathogenesis of Autoimmunity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 1007

Editors


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Guest Editor
Allergy and Clinical Immunology, The Technion-Faculty of Medicine, Haifa, Israel
Interests: autoimmunity; regulatory mechanisms; atopic dermatitis; chronic spontaneous urticaria
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
The Unit of Proteomics and Flow Cytometry, Division of Allergy and Clinical Immunology, Bnai-Zion Medical Center, Faculty of Medicine, Technion, Haifa, Israel
Interests: immune-mediated-inflammation; semaphorins; regulatory molecules; chronic spontaneous urticaria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immune-mediated diseases, specifically autoimmune, develop when regulatory mechanisms fail to maintain self-tolerance. Immune regulation is classically maintained by the proper function of T and B regulatory cells, which prevent immune inflammation and keep a normal balance between inflammatory and inhibitory cytokines. During the last decade, attention was switched towards the role of many membrane-bound regulatory molecules on both B and T regulatory cells, such as CD72, semaphorin3A (sema3A), PD1-PDL1 pairs, LAG3 and others.  Moreover, soluble regulatory molecules such as sol CD72, sol sema3A, sol CTLA-4, sol LAG3 and others are intensively investigated, becoming a hot issue with the aim of obtaining a better understanding of their pathogenesis of autoimmunity. With respect to all of the above, new therapeutic approaches are introduced, aiming to target these molecules and achieve better outcomes for all immune-mediated diseases. In this Special Issue, we invite contributors to submit relevant original papers or reviews covering new aspects and highlighting new ideas to enhance our understanding of these regulatory molecules.

Prof. Dr. Elias Toubi
Prof. Dr. Vadasz Zahava
Guest Editors

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Keywords

  • immune regulation
  • soluble regulatory molecules
  • autoimmunity

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Published Papers (1 paper)

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Research

18 pages, 3154 KB  
Article
Lactate Enhances CD8+ T Cell Cytotoxicity Through H3K9la Upregulation to Drive Vitiligo Pathogenesis
by Hang Yin, Yufei Xu, Luling Huang, Yuxuan Qian, Qing Zhu and Jianru Chen
Int. J. Mol. Sci. 2026, 27(9), 3795; https://doi.org/10.3390/ijms27093795 - 24 Apr 2026
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Abstract
Vitiligo is characterized by epidermal melanocyte destruction, with autoreactive CD8+ T cells playing a central pathogenic role, yet the mechanisms driving their hyperactivation remain unclear. Lactate has emerged as a key immunometabolite that functions as both a signaling molecule and an epigenetic [...] Read more.
Vitiligo is characterized by epidermal melanocyte destruction, with autoreactive CD8+ T cells playing a central pathogenic role, yet the mechanisms driving their hyperactivation remain unclear. Lactate has emerged as a key immunometabolite that functions as both a signaling molecule and an epigenetic modulator via protein lactylation. Nevertheless, the role of lactate in vitiligo pathogenesis has not been explored. Here, we report that serum lactate levels are significantly elevated in vitiligo patients and correlate positively with disease activity. In a mouse model, lactate administration accelerated vitiligo progression, accompanied by increased CD8+ T cell infiltration and melanocyte destruction in lesional skin. In vitro, lactate enhanced CD8+ T cell effector molecule expression (granzyme B, perforin, IFN-γ, CD107a) and cytotoxic function. Mechanistically, lactate increased global protein lactylation in CD8+ T cells, with marked enrichment at histone H3 lysine 9 (H3K9). H3K9 lactylation (H3K9la) was associated with enhanced chromatin accessibility and transcriptional activation of effector genes, as revealed by RNA sequencing and CUT&Tag analyses. Pharmacological inhibition of lactate production or lactylation abrogated these effects. Collectively, our findings identify lactate as a critical driver of CD8+ T cell pathogenicity in vitiligo through H3K9la-mediated epigenetic reprogramming, highlighting lactate metabolism and lactylation as potential therapeutic targets. Full article
(This article belongs to the Special Issue Immune Regulatory Mechanisms in the Pathogenesis of Autoimmunity)
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