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Graft-versus-host Disease

Increased Th17/Treg ratio in chronic liver GVHD

Bone Marrow Transplantation volume 49, pages 539–544 (2014)Cite this article

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Abstract

The contribution of Th17 cells to chronic GVHD (cGVHD) has been demonstrated in cGVHD mouse models. However, their contribution to human liver cGVHD remains unclear. We evaluated Th17 cells in biopsies from a cohort of 17 patients with liver cGVHD. We observed a significant increase in Th17 cells in the liver of patients with cGVHD, as demonstrated by an increase in CCR6+, CD161+ and RORγt+ T cells (P=0.03, P=0.0001 and P=0.03, respectively). We also assessed the presence of Th1 and regulatory (Treg) T cells: the numbers of Th1 and Treg cells were very low, with no difference between the two groups (P=0.88 and P=0.12, respectively). Furthermore, Th17/Th1 and Th17/Treg ratios were significantly increased in the liver of patients with liver cGVHD (P=0.005 and P=0.002, respectively). This study provides evidence for an infiltration by Th17 cells in the liver of patients with cGVHD and an increased Th17/Treg ratio, suggesting a defect in the regulatory mechanism driven by Treg cells or an inappropriate activation of effectors cells, especially Th17 cells, or both mechanisms, in human liver cGVHD.

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Acknowledgements

The authors acknowledge the technical and logistical support of S Blandin, C Deleine, S Leclercq and V Dehame. We also thank the nursing staff for providing excellent care for our patients, and the following physicians: N Blin, A Clavert, V Dubruille, T Gastinne, JL Harousseau, S Le Gouill, B Mahe, F Mechinaud and F Rialland for their dedicated patient care. FM and EB were supported by educational grants from the ‘Association for Training, Education and Research in Hematology, Immunology and Transplantation’ (ATERHIT). This work was supported by funding as part of the CESTI project (Nantes, France). We also thank the ‘Région Pays de Loire’, the ‘Association pour la Recherche sur le Cancer (ARC; grant #3175 to MM and BG)’, the ‘Fondation de France’, the ‘Fondation contre la Leucémie’, the ‘Agence de Biomédecine’, the ‘Association CentpourSang la Vie’, the ‘Association Laurette Fuguain’, the IRGHET and the ‘Ligue Contre le Cancer’ (Comités Grand-Ouest) for their generous and continuous support of our clinical and basic research work. Our transplant programs are supported by several grants from the French national cancer institute (PHRC, INCa to MM). The authors acknowledge the continuous support of the cell banking facility (‘tumorotheque’) of the CHU de Nantes.

Author contributions

All authors listed in the manuscript have contributed substantially to this work: conception and design: Florent Malard, Mohamad Mohty, Béatrice Gaugler, Céline Bossard; financial support: Mohamad Mohty, Marc Grégoire; administrative and logistical support: Jean-François Mosnier, Mohamad Mohty, Béatrice Gaugler, Marc Grégoire; provision of study materials and patients care: Eolia Brissot, Patrice Chevallier, Thierry Guillaume, Jacques Delaunay, Philippe Moreau, Mohamad Mohty; experimental work: Florent Malard, Céline Bossard; collection and assembly of clinical data: Florent Malard, Eolia Brissot, Mohamad Mohty; data analysis and interpretation: Florent Malard, Céline Bossard, Mohamad Mohty, Béatrice Gaugler; manuscript writing: Florent Malard, Mohamad Mohty, Céline Bossard, Béatrice Gaugler; final approval of manuscript: all co-authors.

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Author notes

  1. M Mohty

    Present address: Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France; Universite Pierre et Marie Curie, Paris, France; and INSERM, UMRs 938, Paris, France.,

Authors and Affiliations

  1. CRNCA, UMR 892 INSERM - 6299 CNRS, Nantes, France

    F Malard, E Brissot, P Moreau, M Grégoire & M Mohty

  2. Service d’Hématologie Clinique, Centre Hospitalier et Universitaire (CHU), Université de Nantes, Nantes, France

    F Malard, E Brissot, P Chevallier, T Guillaume, J Delaunay, P Moreau & M Mohty

  3. EA4273 Biometadys, Faculté de médecine, Université de Nantes, Nantes, France

    C Bossard & J-F Mosnier

  4. Service d’Anatomie et Cytologie Pathologique, CHU de Nantes, Nantes, France

    C Bossard & J-F Mosnier

  5. Centre d’Investigation Clinique en Cancérologie (CI2C), Nantes, France

    P Moreau

  6. INSERM UMR 1098, Besançon, France

    B Gaugler

  7. Université de Franche-Comté, Besançon, France

    B Gaugler

  8. EFS Bourgogne Franche-Comté, 25020 Besançon Cedex, Besançon, France

    B Gaugler

  9. Centre d’Investigation Clinique en Biothérapie CBT506, Plateforme de Biomonitoring, Besançon, France

    B Gaugler

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Correspondence to M Mohty.

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Malard, F., Bossard, C., Brissot, E. et al. Increased Th17/Treg ratio in chronic liver GVHD. Bone Marrow Transplant 49, 539–544 (2014). https://doi.org/10.1038/bmt.2013.215

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