{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified miR‐4281—a microRNA uniquely expressed in hominids—as a critical transcriptional enhancer of FOXP3. miR‐4281 directly interacts with the TATA‐box motif in the human FOXP3 promoter, markedly increasing FOXP3 expression. This upregulation accelerates the differentiation of naïve T cells into induced regulatory T cells (iTregs) with potent immune suppressor functions, thereby contributing to the attenuation of graft‐versus‐host disease. Moreover, the IL‐2/STAT5 pathway not only supports conventional FOXP3 regulation but also enhances the expression of the miR‐4281 precursor gene, establishing a positive regulatory loop that reinforces iTreg stability and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe identification of miR‐4281’s role in directly uplifting FOXP3 transcription positions it as a promising candidate for therapeutic strategies aimed at modulating immune tolerance. When combined with TGF‐β and IL‐2, synthetic miR‐4281 produces iTregs that are more stable and functionally robust than those induced by cytokine stimulation alone. This mechanism suggests that targeted upregulation of miR‐4281 could serve as a novel approach to control dysregulated immune responses in autoimmune conditions and improve outcomes in clinical transplant settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yiwen Zhang, Weiwei Liu, Yingshi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Cellular MicroRNA Facilitates Regulatory T Lymphocyte Development by Targeting the "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "FOXP3"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Promoter TATA-Box Motif."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1700196"}], "href": "https://doi.org/10.4049/jimmunol.1700196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29282311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29282311"}]}]}]}