Interleukin Networks in GVHD: Mechanistic Crosstalk, Therapeutic Targeting, and Emerging Paradigms

Graft-versus-host disease (GVHD) is one of the most prevalent and life-threatening complications that can arise following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD occurs when immune cells—primarily T cells—from the graft recognize host cells as foreign entities and initiate an immune response against host tissues. This immune reaction generally involves a diverse array of cytokines, including interleukins (ILs), which play a pivotal role in modulating the immune response, promoting inflammation, and sustaining immune tolerance. Members of the interleukin family are not only directly involved in the activation, proliferation, and differentiation of T cells but also regulate inflammatory responses and the migration of immune cells. Consequently, they significantly influence both the clinical manifestations and prognosis of GVHD. The objective of this study is to review recent advancements in research concerning interleukins and their role in the pathogenesis of GVHD. This study aims to elucidate how interleukins contribute to immune regulation, inflammatory responses, and clinical manifestations. Furthermore, we will discuss their potential as therapeutic targets, with the intention of providing novel insights and strategies for the clinical management of GVHD.