{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSP140 is a leukocyte‐restricted nuclear protein harboring epigenetic “reader” domains that regulate transcription and are implicated in intrinsic immunity. In nonpermissive cells for HIV‐1 infection, SP140 localizes to nuclear bodies and relocalizes upon infection, suggesting that it may participate in antiviral defense mechanisms by interacting with viral factors (for example, HIV-1 Vif) and modulating subnuclear compartmentalization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have linked SP140 polymorphisms and alternatively spliced isoforms with several immune-mediated diseases, including chronic lymphocytic leukemia, multiple sclerosis, and Crohn’s disease. Variants in the SP140 locus alter splicing—such as skipping of exon 7—and result in reduced full-length protein expression. These molecular changes are associated with modulation of inflammatory responses, including NF-κB–driven cytokine production, thereby contributing to disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies in myeloid cells further support SP140’s role as a key regulator of immune gene programs. In macrophages, SP140 acts as a repressor of topoisomerases to maintain heterochromatic regions and proper transcriptional silencing, which is critical for appropriate inflammatory responses to pathogens. This regulation helps to ensure effective antimicrobial defense in contexts such as Mycobacterium tuberculosis infection, modulates the activity of tumor-associated macrophages, and is involved in the control of intestinal inflammation by shaping phagocytic and antimicrobial programs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Navid Madani, Robert Millette, Emily J Platt, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SP140 regulates the expression of immune-related genes associated with multiple sclerosis and other autoimmune diseases by NF-κB inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddy284"}], "href": "https://doi.org/10.1093/hmg/ddy284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30102396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30102396"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hajera Amatullah, Isabella Fraschilla, Sreehaas Digumarthi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic reader SP140 loss of function drives Crohn's disease due to uncontrolled macrophage topoisomerases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2022.06.048"}], "href": "https://doi.org/10.1016/j.cell.2022.06.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35952671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35952671"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kranthi Kiran Kishore Tanagala, Joshua Morin-Baxter, Richard Carvajal, et al. 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