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The Role of Interleukin-2 in Graft-Versus-Host Disease Pathogenesis, Prevention and Therapy Publisher Pubmed



Najaf Khosravi H1, 2 ; Razi S2, 3 ; Rezaei N3, 4, 5
Authors
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Authors Affiliations
  1. 1. Royan Institute for Stem Cell Biology and Technology, Tehran, Iran
  2. 2. Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  3. 3. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden

Source: Cytokine Published:2024


Abstract

Graft-versus-host disease (GVHD) is a significant complication following allogeneic hematopoietic cell transplantation (allo-HCT), posing substantial risks to patient survival. In the late follow-up phase of transplanted patients, GVHD is also a major cause of morbidity and disability, mostly due to low response to first-line steroids and the lack of effective standard therapies in the second line. This review provides a description of GVHD pathogenesis, with a focus on the central role of Interleukin-2 (IL-2). IL-2 is one of the critical mediators in the complex pathogenesis of GVHD, contributing to the intricate balance between regulatory T cells (Tregs) and effector T cells (Teffs). Due to this pivotal role, several studies investigate the potential of IL-2 as a therapeutic option for GVHD management. We discuss the outcomes of low-dose IL-2 therapies and their impact on Treg proliferation and steroid dependency reduction. Additionally, the effects of combining IL-2 with other treatments, such as extracorporeal photopheresis (ECP) and Treg-enriched lymphocyte infusions, are highlighted. Novel approaches, including modified IL-2 complexes and IL-2 receptor blockade, are explored for their potential in selectively enhancing Treg function and limiting Teff activation. The evolving understanding of IL-2′s pivotal role in immune regulation presents promising prospects for applying treatment and prevention strategies for GVHD. © 2024 Elsevier Ltd
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