Human gut microbiota-reactive DP8a regulatory T cells prevent acute graft-versus-host disease in a CD73-dependent manner - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue JCI Insight Année : 2024

Human gut microbiota-reactive DP8a regulatory T cells prevent acute graft-versus-host disease in a CD73-dependent manner

Résumé

Graft-versus-host disease (GvHD) is a life-threatening complication frequently occurring following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since gut microbiota and regulatory T cells (Tregs) are believed to play roles in GvHD prevention, we investigated whether DP8a Tregs, which we have previously described to harbor a TCR-specificity for the gut commensal Faecalibacterium prausnitzii, could protect against GvHD, thereby linking microbiota and its effect on GvHD. We observed a decrease in CD73+ DP8α Treg frequency in allo-HSCT patients at 1-month post-transplantation, which was associated with aGvHD development at 1-month post-transplantation, as compared to aGvHD-free patients, without being correlated to hematological disease's relapse. Importantly, CD73 activity was shown to be critical for DP8αTreg suppressive function. Moreover, the frequency of host-reactive DP8α Tregs was also lower in aGvHD patients, as compared to aGvHD-free patients, which could embody a protective mechanism responsible for the maintenance of these cell subset in GvHD-free patients. We also showed that human DP8α Tregs protected mice against xeno-GvHD through limiting deleterious inflammation and preserving gut integrity. Altogether, these results demonstrated that human DP8α Tregs mediate aGvHD prevention in a CD73-dependent manner, likely through host-reactivity, advocating for the use of these cells for the development of innovative therapeutic strategies to preclude aGvHD-related inflammation.
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inserm-04666958 , version 1 (07-10-2024)

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Emmanuelle Godefroy, Patrice Chevallier, Fabienne Haspot, Caroline Vignes, Véronique Daguin, et al.. Human gut microbiota-reactive DP8a regulatory T cells prevent acute graft-versus-host disease in a CD73-dependent manner. JCI Insight, 2024, pp.e179458. ⟨10.1172/jci.insight.179458⟩. ⟨inserm-04666958⟩
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