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| Status |
Public on Aug 29, 2022 |
| Title |
IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4+Foxp3+ regulatory T lymphocytes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell
precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg
apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had
recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the
involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. In three-week-old mice, when
substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed
Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no
recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than
deficiency in IL-15. IL-2 and IL-15 differentially modulated the CD25, GITR, OX40, and CD73-phenotypes of thymus-egress-competent
and periphery-seeding Treg. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon
transfer into Treg-less Foxp3sf mice, thymus-exit-competent Treg from IL-2- (and to a lesser extent IL-15-) deficient mice
suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant
quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.
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| Overall design |
CD4+CD8−Thy1.1+GFP+ thymic Treg (10^5) were FACS sorted from individual three week-old wt (n=4), Il2o (n=4), or Il15o (n=4) Rag2-Gfp Foxp3-Thy1a Tcra +/o Kaa TCRbeta-transgenic B6 mice.
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| Contributor(s) |
Apert C, Galindo-Albarran A, Castan S, Detraves C, Michaud H, McJannett N, Haegeman B, Fillatreau S, Malissen B, Holländer G, Žuklys S, Santamaria J, Joffre O, Romagnoli P, van Meerwijk JP |
| Citation(s) |
36159793 |
| Submission date |
Jun 29, 2020 |
| Last update date |
Oct 04, 2022 |
| Contact name |
Joost Van Meerwijk |
| E-mail(s) |
Joost.van-Meerwijk@inserm.fr
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| Phone |
0562748381
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| Organization name |
INSERM
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| Department |
CPTP U1043
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| Lab |
Joost Van Meerwijk Eq1
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| Street address |
CHU Purpan BP 3028
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| City |
Toulouse |
| State/province |
HG |
| ZIP/Postal code |
31024 |
| Country |
France |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA642815 |
| SRA |
SRP269206 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE153484_RAW.tar |
840.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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