UNC93B1 is essential for the stability and endosomal trafficking of nucleic-acid sensing Toll-like receptors (TLRs) including TLR7 and TLR8. Increased TLR7 responses are associated with lupus autoimmunity in both mice and humans. In a recent article, Al-Azab et al. demonstrate the role of a variant of UNC93B1 (p.V117L) in the induction of pediatric systemic lupus erythematosus in patients and in mice through TLR7/8 hyperresponsiveness. They also highlight a potential role for the pharmacological inhibition of interleukin-1 receptor–associated kinase (IRAK) 1 and/or 4 in ameliorating disease.
{"title":"UNCovering new causes of monogenic systemic lupus erythematosus","authors":"Julia I Ellyard, Michael P Gantier","doi":"10.1111/imcb.12807","DOIUrl":"10.1111/imcb.12807","url":null,"abstract":"<p>UNC93B1 is essential for the stability and endosomal trafficking of nucleic-acid sensing Toll-like receptors (TLRs) including TLR7 and TLR8. Increased TLR7 responses are associated with lupus autoimmunity in both mice and humans. In a recent article, Al-Azab <i>et al.</i> demonstrate the role of a variant of <i>UNC93B1</i> (p.V117L) in the induction of pediatric systemic lupus erythematosus in patients and in mice through TLR7/8 hyperresponsiveness. They also highlight a potential role for the pharmacological inhibition of interleukin-1 receptor–associated kinase (IRAK) 1 and/or 4 in ameliorating disease.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this article, we discuss new insights into the distinct mechanisms for V(D)J recombination for different immunoglobulin loci. This follows the recent revelation that recombination signal sequences (RSS) within the IGKV locus have evolved to be more efficient mediators of recombination activating gene (RAG) recombination compared to the same elements in the IGH locus. This difference in RSS strength is proposed to be driven by different molecular mechanisms for RAG-mediated recombination between the two loci.