BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Alloimmunity and Transplantation
This article is part of the Research TopicLocalized Immunomodulation Approaches for Transplantation ToleranceView all 6 articles
TSG-6 Expression Distinguishes Rejected and Non-Rejected Human Lung Transplants: A Retrospective Study
Provisionally accepted
- University of Maryland, Baltimore, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Lung transplantation (LTx) remains the definitive treatment for select end-stage pulmonary diseases, yet early graft failure due to acute rejection continues to compromise long-term outcomes. Tissue injury and insufficient reparative responses in the immediate post-transplant period contribute to this vulnerability. Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) is a multifunctional anti-inflammatory and tissue-protective protein known to facilitate resolution of inflammation and extracellular matrix remodeling, but its role in human LTx remains undefined. In this retrospective study, we examined TSG-6 expression in transbronchial biopsies from two matched cohorts of LTx recipients—those with histopathologically confirmed acute rejection (n = 6) and those without rejection (n = 6)—within the first postoperative month. Immunofluorescence analysis revealed significantly elevated TSG-6 expression in non-rejected grafts across two metrics: whole-biopsy staining intensity (~15–40 units vs. ~0–10 units, p < 0.01) and percentage of TSG-6–positive cells (~90% vs. ~30%, p < 0.01). Scatter plot visualization confirmed a clear separation between groups, suggesting that elevated TSG-6 expression—both in total tissue and per-cell prevalence—is strongly associated with the absence of acute rejection and may reflect a reparative immune phenotype. Despite the limited sample size, the consistency and magnitude of the effect (Cohen's d ≈ 4.7) underscore the biological relevance of TSG-6 in early graft stability. Our data establish a novel link between increased TSG-6 expression and diminished acute rejection in human lung allografts, suggesting that TSG-6 may actively modulate alloimmune responses and serve as both a marker of graft stability and a candidate for therapeutic intervention.
Keywords: TSG-6 (Tumor Necrosis Factor-Stimulated Gene-6), Inflammation, Immune Tolerance, acute rejection, Lung Transplantation
Received: 13 Aug 2025; Accepted: 13 Nov 2025.
Copyright: © 2025 Khan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mohammad Afzal Khan, mafzlkhan@gmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.