Immunological challenges in lung transplantation: Clinical and experimental advances

Progress in the field requires a simultaneous view of the clinical and experimental landscape. Breakthroughs in preclinical models have reshaped our understanding of alloimmunity, trained innate immunity, and regulatory T cell biology, yet translation into clinical practice remains slow. At the same time, real-world data from transplant centres are surfacing patterns in rejection, infection, and immune dysregulation that experimental systems have not yet fully explained. Closing this gap is one of the most pressing challenges in transplant immunology.

By integrating experimental findings with clinical observations, this Topic aims to surface both the mechanisms driving poor graft outcomes and the therapeutic strategies most likely to change them. It is particularly timely given rapid advances in cell-based therapies, machine perfusion technology, and single-cell immunoprofiling, all of which are opening new windows into lung allograft biology.

This Research Topic bringstogether contributions from clinicians, immunologists, and translational researchers to address the full spectrum of immunological challenges in lung transplantation. We welcome articles on themes including, but not limited to:

• Primary graft dysfunction and ischemia-reperfusion injury: innate immune activation, damage-associated molecular patterns, and early graft failure
• Acute and chronic rejection: cellular and antibody-mediated mechanisms, donor-specific antibodies, and chronic lung allograft dysfunction (CLAD)
• Infection and immune dysregulation: the impact of bacterial, viral (including CMV), and fungal infections on alloimmune responses, and the role of the airway microbiome in shaping graft outcomes
• Immune tolerance and immunomodulation: regulatory T cell therapies, complement inhibition, co-stimulation blockade, and other emerging strategies to promote long-term graft acceptance
• Preclinical models and translational insights: animal models, ex vivo lung perfusion platforms, and organoid systems that bridge bench findings to clinical application
• Biomarkers and clinical monitoring: non-invasive tools for early detection of rejection and immune activation