Immune Tolerance in Transplantation: Mechanisms and Therapeutic Strategies

A Special Issue of Biomedicines (ISSN 2227-9059) belonging to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 28 February 2027 | Viewed by 283

Editors


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Guest Editor
Department of Anesthesiology and Intensive Therapy, Silesian Centre for Heart Diseases, Medical University of Silesia, Katowice, Poland
Interests: intensive care; cardiac anesthesia; cardiothoracic transplantation; immune tolerance

E-Mail Website
Guest Editor
Department of Anesthesiology and Intensive Therapy, Silesian Centre for Heart Diseases, Medical University of Silesia, Katowice, Poland
Interests: intensive care; heart failure; mechanical circulatory support; heart transplantation; cardiac anesthesia
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Special Issue Information

Dear Colleagues,

This Special Issue, “Immune Tolerance in Transplantation: Mechanisms and Therapeutic Strategies”, highlights the increasing understanding of how the immune system can be guided to accept transplanted organs without the need for lifelong immunosuppression. Although current treatments have consistently improved short-term outcomes, long-term survival and quality of life are still limited by chronic rejection, treatment-related toxicities, and complications arising from prolonged immunosuppression.

Tolerance in transplantation is not a passive state but rather reflects a dynamic balance between regulatory immune pathways and controlled alloimmune activation. Research increasingly concentrates on regulatory cell populations. There are conventional and unconventional regulatory T cells, regulatory B cells, and tolerogenic innate subsets, which can modulate inflammatory responses and support graft stability. These mechanisms have been described experimentally and in early clinical translational studies, highlighting their potential significance for strategies that promote tolerance.

Recent studies have emphasised immune checkpoint pathways as crucial regulators of T-cell activity. Molecules like CTLA-4, PD-1, TIGIT, TIM-3, and LAG-3 play roles in balancing between effector and regulatory responses within the graft environment. A deeper understanding of these pathways in transplant patients could enable more precise immunomodulatory strategies that strengthen protective immunity instead of suppressing it broadly.

Another area of progress comes from translational concepts aimed at adjusting peripheral immune activation. These include interventions focusing on selective co-stimulation blockade, modulation of metabolic states in effector lymphocytes, and strategies designed to support regulatory signatures within the graft. Although these approaches are still evolving, they show potential ways to maintain long-term graft acceptance while reducing overall exposure to systemic immunosuppression.

These advances are based on the common goal of making immunosuppression safer, more targeted, and personalised. Ongoing progress in immunomonitoring techniques, identifying reliable biomarkers, and deepening our understanding of intragraft regulatory processes could help in identifying patients who can safely undergo gradual immunosuppression reduction without risking graft function.

This Special Issue welcomes contributions that explore the mechanistic foundations of tolerance in transplantation, translational strategies to enhance immunological stability, and clinically applicable methods to improve long-term graft survival.

Dr. Marta Wajda-Pokrontka
Dr. Pawel Nadziakiewicz
Guest Editors

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Keywords

  • donor-specific tolerance
  • transplant immunoregulation
  • solid organ transplantation
  • immunosuppressive therapy optimisation
  • immune monitoring in transplant recipients
  • graft stability and long-term outcomes
  • regulatory immune networks

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Published Papers (1 paper)

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Research

12 pages, 1902 KB  
Article
Calcineurin Inhibitor-Based Triple Immunosuppressive Therapy Induces Profibrotic Changes in the Jejunal Mucosa of Male Rats: A Digital Image Analysis of Collagen Fibers
by Kamila Szumilas, Aleksandra Wilk, Paweł Szumilas, Karolina Klimek and Karolina Kędzierska-Kapuza
Biomedicines 2026, 14(9), 2064; https://doi.org/10.3390/biomedicines14092064 - 15 Sep 2026
Abstract
Background/Objectives: Long-term immunosuppressive therapy administered to solid organ transplant recipients may induce adverse effects in various tissues, including the gastrointestinal tract. The aim of the present study was to evaluate the influence of prolonged treatment with calcineurin inhibitor (CNI)-based triple immunosuppressive regimens on [...] Read more.
Background/Objectives: Long-term immunosuppressive therapy administered to solid organ transplant recipients may induce adverse effects in various tissues, including the gastrointestinal tract. The aim of the present study was to evaluate the influence of prolonged treatment with calcineurin inhibitor (CNI)-based triple immunosuppressive regimens on the morphology of the jejunal mucosa in male rats. Particular attention was paid to fibrotic changes occurring within the mucosal connective tissue, including the intestinal villi and lamina propria. Methods: Animals were treated for six months with regimens containing either cyclosporine A (CyA) or tacrolimus (TAC) in combination with rapamycin and prednisone. To assess the content of collagen fibers, jejunal sections were stained using the Mallory trichrome method and subsequently subjected to quantitative digital image analysis. Results: Histological examination demonstrated increased collagen deposition in the jejunal mucosa of rats receiving immunosuppressive treatment compared with the control group. Quantitative analysis confirmed an increase in collagen fiber content, indicating enhanced extracellular matrix accumulation and changes consistent with fibrotic remodeling of the mucosal connective tissue. The highest collagen fiber content was observed in animals treated with the cyclosporine-based regimen. Conclusions: These findings suggest that long-term administration of CNI-based triple immunosuppressive therapy may be associated with changes consistent with fibrotic remodeling of the jejunal mucosa. The present study provides novel data on the effects of clinically relevant multidrug immunosuppressive protocols, whereas most previous experimental studies investigating the effects of immunosuppressive agents have focused on single-drug exposure in animal models or in vitro systems. Full article
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