Human gut microbiota-reactive DP8α Tregs prevent acute graft-versus-host disease in a CD73-dependent manner.

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 DP8α Tregs, which we have previously described to harbor a T cell receptor specificity for the gut commensal Faecalibacterium prausnitzii, could protect against GvHD, thereby linking the microbiota and its effect on GvHD. We observed a decrease in CD73+ DP8α Treg frequency in allo-HSCT patients 1 month after transplantation, which was associated with acute GvHD (aGvHD) development at 1 month after transplantation, as compared with aGvHD-free patients, without being correlated to hematological disease relapse. Importantly, CD73 activity was shown to be critical for DP8α Treg suppressive function. Moreover, the frequency of host-reactive DP8α Tregs was also lower in aGvHD patients, as compared with aGvHD-free patients, which could embody a protective mechanism responsible for the maintenance of this cell subset in GvHD-free patients. We also showed that human DP8α Tregs protected mice against xenogeneic 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.

Slime molds response to carbon nanotubes exposure: from internalization to behavior.

Carbon nanotubes (CNTs) offer attractive opportunities due to their physical, electrical, mechanical, optical, and thermal properties. They are used in a wide range of applications and are found in numerous consumer products. On the downside, their increasing presence in the environment poses potential threats to living organisms and ecosystems. The aim of this study was to evaluate the toxicity of double-walled carbon nanotubes (DWCNTs) on a new model system: the acellular slime mold Physarum polycephalum. Despite its ecological significance, its simplicity of organization, and its behavioral complexity, exposure of such organisms to nanoparticles has been poorly investigated. Slime molds were exposed to DWCNTs using three routes of exposure (topical, food, environment). We first demonstrated that DWCNTs were rapidly internalized by slime molds especially when DWCNTs were mixed with the food or spread out in the environment. Secondly, we showed that a 6-week exposure to DWCNTs did not lead to bioaccumulation nor did it lead to persistence in the slime molds when they entered a resting stage. Thirdly, we revealed that 2 days following exposure, DWCNTs were almost entirely excreted from the slime molds. Lastly, we uncovered that DWCNTs exposure altered the migration speed, the pseudopods formation, and the expansion rate of the slime molds. Our results extend our current knowledge of CNTs cytotoxicity and introduce P. polycephalum as an ideal organism for nanotoxicology.