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The unfolded-protein-response sensor IRE-1α regulates the function of CD8α+ dendritic cells.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: New York, NY : Nature America Inc. c2000-
    • الموضوع:
      Protein Unfolding*; Cross-Priming/*immunology ; DNA-Binding Proteins/*immunology ; Dendritic Cells/*immunology ; Endoribonucleases/*immunology ; Protein Serine-Threonine Kinases/*immunology ; Transcription Factors/*immunology ; Unfolded Protein Response/*immunology; Animals ; Antigen Presentation/immunology ; CD8 Antigens/immunology ; CD8 Antigens/metabolism ; DNA-Binding Proteins/metabolism ; Dendritic Cells/metabolism ; Endoplasmic Reticulum/immunology ; Endoribonucleases/metabolism ; Feedback, Physiological/physiology ; Homeostasis/immunology ; Immunoblotting ; Immunohistochemistry ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron ; Oligonucleotide Array Sequence Analysis ; Protein Serine-Threonine Kinases/metabolism ; Regulatory Factor X Transcription Factors ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/metabolism ; X-Box Binding Protein 1
    • نبذة مختصرة :
      The role of the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in homeostasis of the immune system is incompletely understood. Here we found that dendritic cells (DCs) constitutively activated the UPR sensor IRE-1α and its target, the transcription factor XBP-1, in the absence of ER stress. Loss of XBP-1 in CD11c+ cells led to defects in phenotype, ER homeostasis and antigen presentation by CD8α+ conventional DCs, yet the closely related CD11b+ DCs were unaffected. Whereas the dysregulated ER in XBP-1-deficient DCs resulted from loss of XBP-1 transcriptional activity, the phenotypic and functional defects resulted from regulated IRE-1α-dependent degradation (RIDD) of mRNAs, including those encoding CD18 integrins and components of the major histocompatibility complex (MHC) class I machinery. Thus, a precisely regulated feedback circuit involving IRE-1α and XBP-1 controls the homeostasis of CD8α+ conventional DCs.
    • Comments:
      Comment in: Nat Rev Immunol. 2014 Mar;14(3):135. (PMID: 24525837)
      Comment in: Nat Immunol. 2014 Mar;15(3):213-5. (PMID: 24549063)
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    • Molecular Sequence:
      GEO GSE52857
    • الرقم المعرف:
      0 (CD8 Antigens)
      0 (CD8alpha antigen)
      0 (DNA-Binding Proteins)
      0 (Regulatory Factor X Transcription Factors)
      0 (Transcription Factors)
      0 (X-Box Binding Protein 1)
      0 (Xbp1 protein, mouse)
      EC 2.7.11.1 (Ern1 protein, mouse)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
      EC 3.1.- (Endoribonucleases)
    • الموضوع:
      Date Created: 20140121 Date Completed: 20140423 Latest Revision: 20211203
    • الموضوع:
      20240829
    • الرقم المعرف:
      10.1038/ni.2808
    • الرقم المعرف:
      24441789