{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Basic leucine zipper ATF‐like transcription factor 2 (BATF2) is an interferon‐inducible member of the AP‐1 family that plays multifaceted roles in regulating both immunity and tumor suppression. In the immune system, BATF2 is up‐regulated upon cytokine stimulation and contributes to the modulation of innate immune cell differentiation and activation. For instance, BATF2 has been implicated in alternative developmental pathways of CD8α⁺ dendritic cells during infection, acting in concert with related BATF family members to fine‐tune effector responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In macrophages and hematopoietic stem/progenitor cells, BATF2 regulates inflammatory gene expression and promotes appropriate terminal differentiation upon IFN‐γ stimulation, thereby influencing host resistance against intracellular pathogens including Mycobacterium tuberculosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, BATF2 expressed in intestinal innate myeloid populations serves to suppress excessive IL‐23 production and subsequent T‐cell–mediated pathology, thus maintaining mucosal homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, BATF2 functions as a tumor suppressor in a variety of malignancies. Its expression has been found to be down‐regulated in colorectal, hepatocellular, oral tongue, gastric, and breast cancers, among others, where loss of BATF2 is associated with increased tumor progression, metastasis, chemoresistance, and poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Mechanistically, BATF2 exerts its anti‐tumor activities by antagonizing oncogenic pathways including MET and Wnt/β‐catenin signaling, thereby promoting apoptosis, arresting the cell cycle, and suppressing epithelial–mesenchymal transition (EMT) in glioblastoma and other cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, higher levels of BATF2 correlate with favorable prognoses in breast cancer patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies have revealed that BATF2 can modulate transcriptional programs beyond conventional gene regulation. For example, BATF2 has been shown to prime satellite DNA transcription, which may have implications for genomic stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In autoimmune and inflammatory settings, altered BATF2 expression is linked to dysregulated T‐helper cell differentiation (favoring Th1 and regulatory T cells while limiting Th17 responses in conditions such as clinically amyopathic dermatomyositis) and may serve as a biomarker for therapeutic responsiveness in rheumatoid arthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In systemic lupus erythematosus, BATF2 forms part of a broader transcriptional network regulated by interferon‐stimulated kinases, further underscoring its role in immune homeostasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", while its expression also contributes to distinguishing active tuberculosis in individuals with HIV co‐infection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Finally, by suppressing activator protein‐1 (AP‐1) activity, BATF2 helps reverse drug resistance in gastric cancer cells, demonstrating its potential as a therapeutic target to sensitize tumors to chemotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight BATF2 as a pivotal regulatory factor whose functions span from orchestrating pathogen defense and maintaining immune equilibrium to inhibiting oncogenic processes and overcoming chemotherapy resistance.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Roxane Tussiwand, Wan-Ling Lee, Theresa L Murphy, et al. 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