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Series GSE253540 Query DataSets for GSE253540
Status Public on Jan 23, 2024
Title Treg cells from human blood differentiate into non-lymphoid tissue-resident effector cells upon TNFR2 costimulation
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Regulatory T (Treg) cells can facilitate transplant tolerance and attenuate autoimmune- and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg cell expansion and function in vivo and to create therapeutic Treg cell products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naïve, thymus-derived (t)Treg cells from human blood that promotes their differentiation into non-lymphoid tissue (NLT)-resident effector Treg cells, without Th-like polarization. In contrast, CD28 costimulation maintains a lymphoid tissue (LT)-resident Treg cell phenotype. We base this conclusion on transcriptome and proteome analysis of TNFR2- and CD28-costimulated CD4+ tTreg cells and conventional T (Tconv) cells, followed by bioinformatic comparison with published transcriptomic Treg cell signatures from NLT and LT in health and disease, including autoimmunity and cancer. These analyses illuminated that TNFR2 costimulation promotes tTreg cell capacity for survival, migration, immunosuppression and tissue regeneration. Functional studies confirmed improved migratory ability of TNFR2-costimulated tTreg cells. Flow cytometry validated the presence of the TNFR2-driven tTreg cell signature in effector/memory Treg cells from the human placenta as opposed to blood. Thus, TNFR2 can be exploited as driver of NLT-resident tTreg cell differentiation for adoptive cell therapy or antibody-based immunomodulation in human disease.
Overall design Whole transcriptome analysis of human naïve conventional and thymus-derived regulatory CD4 T cells that were stimulated with recombinant human IL-2 and anti-CD3 agonistic mAb and costimulated with either anti-CD28 or anti-TNFR2 agonistic mAb for 7 days. Samples are derived from 5 healthy blood donors.
Contributor(s) Mensink M, Borst J
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Submission date Jan 18, 2024
Last update date Jan 23, 2024
Contact name Mark Mensink
Organization name Leiden University Medical Center
Department Immunology
Street address Albinusdreef 2
City Leiden
ZIP/Postal code 2333ZA
Country Netherlands
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (20)
GSM8022800 Tconv_CD28_Donor1
GSM8022801 Tconv_TNFR2_Donor1
GSM8022802 tTreg_CD28_Donor1
BioProject PRJNA1066252

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Supplementary file Size Download File type/resource
GSE253540_RNAseq_processed_data_file_TMM.txt.gz 4.4 Mb (ftp)(http) TXT
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