Molecular signatures of natural killer cells in CMV-associated anterior uveitis, a new type of CMV-induced disease in immunocompetent individuals

Nobuyo Yawata, Mariko Shirane, Kaing Woon, Xinru Lim, Hidenori Tanaka, Yoh Ichi Kawano, Makoto Yawata, Soon Phaik Chee, Jay Siak, Koh Hei Sonoda

Research output: Contribution to journalArticlepeer-review

Abstract

Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed condi-tions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics in-dicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU. Among the immune cell types, natural killer (NK) cells are main responders against CMV. Therefore, we first characterized variants of polymorphic genes that encode differences in CMV-related human NK cell responses (Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I) in 122 CMV-AU patients. The cases were then stratified according to their genetic features and NK cells were analyzed for human CMV-related markers (CD57, KLRG1, NKG2C) by flow cytometry. KIR3DL1 and HLA class I combinations encoding strong receptor–ligand interactions were present at substantially higher frequencies in CMV-AU. In these cases, NK cell profiling revealed expansion of the subset co-expressing CD57 and KLRG1, and together with KIR3DL1 and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves CMV-responding NK cells co-expressing CD57/KLRG1/NKG2C that develop on a genetic background of KIR3DL1/HLA-B allotypes encoding strong receptor–ligand interactions.

Original languageEnglish
Article number3623
JournalInternational journal of molecular sciences
Volume22
Issue number7
DOIs
Publication statusPublished - Apr 1 2021

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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