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Non-classical CD4+CD49b+ regulatory T cells as a better alternative to conventional CD4+CD25+ T cells to dampen arthritis severity

ABSTRACT: Regulatory T (Treg) cells actively control pathological immune responses and immunotherapeutic strategies triggering an increase in the number and/or the function of endogenous Treg cells emerge as a promising therapeutic strategy in autoimmune diseases to restore tolerance. A remarkable heterogeneity in peripheral Treg cells has been evidenced and underscored the need to better characterize them and compare their suppressive function to determine which Treg subset will be optimally suitable for a given clinical situation. We demonstrated that repetitive injections of immature dendritic cells (DC) expand FoxP3-negative CD49b+ Treg cells that display an effector memory phenotype. Transcriptome analysis of ex-vivo isolated Treg-expanded by DC injections contains multiple transcripts of the canonical Treg signature shared mainly by CD25+ but also by other Treg subphenotypes. We provided an in-depth characterization of the CD49b+ Treg cells phenotype underscoring their similarities with CD25+ Treg cells and highlighting some specific expression pattern for several markers including LAG3, KLRG1, CD103, ICOS, CTLA-4 and GZB. Comparison of their suppressive mechanism in vitro and in vivo with that of FoxP3-positive Treg cells provide evidence of their potent suppressive activity in vivo, partly dependent on IL-10 secretion. Altogether our results underscore the therapeutic potential of IL-10 secreting CD49b+ Treg cells in arthritis and strongly suggest that expression of several canonical markers and suppressive function could be FoxP3-independent All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled for sorting, and two to three replicates were generated for all groups. RNA from 2.5-10 x 105 cells was amplified, labeled, and hybridized to Affymetrix M430v2 microarrays.

ORGANISM(S): Mus musculus  

SUBMITTER: Delphine Martire   Paul Chuchana  Anne-Laure Mausset-Bonnefont  Rita Vicente  Paul CHUCHANA  Christian Jorgensen  Julie Quentin  Maïlys Cren  Pascale Louis-Plence 

PROVIDER: E-GEOD-68621 | ArrayExpress | 2015-12-10



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Nonclassical CD4+CD49b+ Regulatory T Cells as a Better Alternative to Conventional CD4+CD25+ T Cells To Dampen Arthritis Severity.

Vicente Rita R   Quentin Julie J   Mausset-Bonnefont Anne-Laure AL   Chuchana Paul P   Martire Delphine D   Cren Maïlys M   Jorgensen Christian C   Louis-Plence Pascale P  

Journal of immunology (Baltimore, Md. : 1950) 20151120 1

Promising immunotherapeutic strategies are emerging to restore tolerance in autoimmune diseases by triggering an increase in the number and/or the function of endogenous regulatory T (Treg) cells, which actively control pathological immune responses. Evidence suggests a remarkable heterogeneity in peripheral Treg cells that warrants their better characterization in terms of phenotype and suppressive function, to determine which subset may be optimally suitable for a given clinical situation. We  ...[more]

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