• Medientyp: E-Artikel
  • Titel: NF‐κB‐inducing kinase contributes to normal development of cortical thymic epithelial cells: its possible role in shaping a proper T‐cell repertoire
  • Beteiligte: Eshima, Koji; Misawa, Kana; Ohashi, Chihiro; Noma, Haruka; Iwabuchi, Kazuya
  • Erschienen: Wiley, 2020
  • Erschienen in: Immunology
  • Sprache: Englisch
  • DOI: 10.1111/imm.13186
  • ISSN: 0019-2805; 1365-2567
  • Schlagwörter: Immunology ; Immunology and Allergy
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  • Beschreibung: <jats:title>Summary</jats:title><jats:p>Nuclear factor (NF)‐κB‐inducing kinase (NIK) is known to be a critical regulator of multiple aspects of the immune response. Although the role of NIK in the development of medullary thymic epithelial cells (mTECs) has been well documented, the impact of NIK on the differentiation and function of cortical thymic epithelial cells (cTECs) remains ambiguous. To investigate the possible involvement of NIK in cTEC differentiation, we have compared the gene expression and function of cTECs from a NIK‐mutant mouse, <jats:italic>aly</jats:italic>mphoplasia (<jats:italic>aly</jats:italic>/<jats:italic>aly</jats:italic>) with those of cTECs from wild‐type (WT) mice. Flow cytometric analyses revealed that expression levels of MHC class II, but not MHC class I or other TEC markers, were higher in <jats:italic>aly</jats:italic>/<jats:italic>aly</jats:italic> cells than in WT cells. Notably, the proportion of MHC class II<jats:sup>hi+</jats:sup> cTECs was elevated in <jats:italic>aly</jats:italic>/<jats:italic>aly</jats:italic> mice. We also demonstrated that expression of <jats:italic>Ccl5</jats:italic> mRNA in the MHC class II<jats:sup>hi+</jats:sup> subset of <jats:italic>aly/aly</jats:italic> cTECs was decreased compared with that in WT cells, implying an abnormal pattern of gene expression in <jats:italic>aly</jats:italic>/<jats:italic>aly</jats:italic> cTECs. Analyses of bone marrow chimera using <jats:italic>aly</jats:italic>/<jats:italic>aly</jats:italic> or <jats:italic>aly</jats:italic>/+ mice as hosts suggested that Vβ usage and CD5 expression on WT T‐cells were altered when they matured in <jats:italic>aly</jats:italic>/<jats:italic>aly</jats:italic> thymi. These results collectively indicate that NIK may be involved in controlling the function of cTEC in selecting a proper T‐cell repertoire.</jats:p>
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