Skip to Main content Skip to Navigation
Journal articles

Microenvironment tailors nTreg structure and function

Abstract : Natural regulatory T cells (nTregs) ensure the control of self-tolerance and are currently used in clinical trials to alleviate autoimmune diseases and graft-versus-host disease after hematopoietic stem cell transfer. Based on CD39/CD26 markers, blood nTreg analysis revealed the presence of five different cell subsets, each representing a distinct stage of maturation. Ex vivo added microenvironmental factors, including IL-2, TGFβ, and PGE2, direct the conversion from naive precursor to immature memory and finally from immature to mature memory cells, the latest being a no-return stage. Phenotypic and genetic characteristics of the subsets illustrate the structural parental maturation between subsets, which further correlates with the expression of regulatory factors. Regarding nTreg functional plasticity, both maturation stage and microenvironmental cytokines condition nTreg activities, which include blockade of autoreactive immune cells by cell-cell contact, Th17 and IL-10 Tr1-like activities, or activation of TCR-stimulating dendritic cell tolerization. Importantly, blood nTreg CD39/CD26 profile remained constant over a 2-y period in healthy persons but varied from person to person. Preliminary data on patients with autoimmune diseases or acute myelogenous leukemia illustrate the potential use of the nTreg CD39/CD26 profile as a blood biomarker to monitor chronic inflammatory diseases. Finally, we confirmed that naive conventional CD4 T cells, TCR-stimulated under a tolerogenic conditioned medium, could be ex vivo reprogrammed to FOXP3 lineage Tregs, and further found that these cells were exclusively committed to suppressive function under all microenvironmental contexts.
Complete list of metadatas

Cited literature [37 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02392153
Contributor : Hélène Le Buanec <>
Submitted on : Tuesday, December 3, 2019 - 7:48:58 PM
Last modification on : Wednesday, October 14, 2020 - 4:02:51 AM
Long-term archiving on: : Wednesday, March 4, 2020 - 9:38:47 PM

File

6298.full.pdf
Publication funded by an institution

Identifiers

Citation

Valérie Schiavon, Sophie Duchez, Mylène Branchtein, Alexandre How-Kit, Charles Cassius, et al.. Microenvironment tailors nTreg structure and function. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2019, 116 (13), pp.6298-6307. ⟨10.1073/pnas.1812471116⟩. ⟨inserm-02392153⟩

Share

Metrics

Record views

405

Files downloads

900