{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nc‐Rel – a member of the NF‑κB transcription factor family – has emerged as a pivotal regulator of immune cell development and function. Multiple studies have demonstrated that c‐Rel is critical for proper dendritic cell maturation and cytokine production (e.g., IL‑12 and IL‑23) as well as for the development and homeostasis of T‐cell subsets including Th1 cells, regulatory T cells, and memory‐supporting populations. In B lymphocytes, c‐Rel is required for antigen receptor–induced cell growth and proliferation via regulation of key cell cycle regulators. These early discoveries underscore its essential role in orchestrating both innate and adaptive immunity by modulating gene expression programs during immune activation and differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, c‐Rel directs transcriptional activation by binding to specific κB elements in the promoters of target genes. Its activity is crucial for chromatin remodeling events that support IL‑2 gene transcription and for the formation of enhanceosomes that govern Foxp3 induction during regulatory T‐cell differentiation. In antigen‐presenting cells, c‐Rel is indispensable for the induction of cytokine subunits (such as those forming IL‑12 and IL‑23) following Toll‑like receptor engagement. Such regulation is achieved through its ability to cooperate with other transcription factors and co‐activators, ensuring the integration of signals from TCR and co-stimulatory molecules. These findings highlight how c‐Rel controls not only the amplitude but also the qualitative nature of immune responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental roles in immune regulation, c‐Rel has been implicated in diverse pathological contexts. In models of autoimmune inflammation and experimental encephalomyelitis, c‐Rel modulates the balance between pathogenic Th subsets and regulatory T cells. In tumorigenesis, aberrant c‐Rel activity contributes to lymphomagenesis and mammary tumor formation through the dysregulation of cell proliferation genes, while in neural contexts, c‐Rel activation downstream of metabotropic receptor signaling promotes neuroprotection against toxic insults. Moreover, post‐transcriptional regulation by microRNAs and interactions with other signaling mediators further refine c‐Rel’s activity, impacting inflammatory cytokine output and cellular survival decisions. Collectively, these studies reveal that c‐Rel functions as a multifaceted transcriptional regulator whose activity must be tightly controlled to maintain immune homeostasis and prevent disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fateh Ouaaz, Joseph Arron, Ye Zheng, et al. 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