{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306188/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306188"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro","description":"T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells play critical roles in regulating the activity of the germinal center (GC), which is essential for the generation of high-affinity antibodies. In the GC, Tfh cells help B cells to proliferate and to differentiate into memory B cells and long-lived plasma cells. In contrast, Tfr cells, a specialized subset of regulatory T cells (Tregs), modulate the humoral immune response by suppressing excessive or autoreactive B-cell activity. Here, we established an in vitro differentiation protocol for mouse CD4⁺ T cells that yielded CXCR5⁺FoxP3⁺ Tfr cells that exhibited a Bcl6hiPD-1hiCD25loGITRint phenotype and were distinct from Treg and Tfh cells. Functionally, in vitro-generated Tfr cells potently suppressed Tfh cell-driven B-cell class switching to IgG1 and downregulated the expression of B-cell costimulatory ligands. While in vitro-generated Bcl6-deficient Tfh cells were impaired in providing help to B cells for efficient class switching to IgG1, in vitro-generated Bcl6-deficient Tfr cells failed to inhibit Tfh cell-driven B-cell class switching to IgG1. Mechanistically, we showed that Tfr cells emerged from FoxP3+ precursors in low-IL-2 environments through a TGF-β- and c-Maf-dependent pathway, allowing for reprogramming and reinforcement of the follicular regulatory cell program in CD4+ T cells in vitro.","dates":{"publication":"2026/07/09"},"accession":"GSE306188","cross_references":{"GSM":["GSM9194504","GSM9194503","GSM9194514","GSM9194506","GSM9194505","GSM9194511","GSM9194510","GSM9194513","GSM9194512","GSM9194508","GSM9194507","GSM9194509"],"GPL":["24247"],"GSE":["306188"],"taxon":["Mus musculus"],"PMID":["[42342921]"]}}