CD38 is a transmembrane protein and ectoenzyme that mainly degrades nicotinamide adenine dinucleotide (NAD+). Studies have revealed increased numbers of CD38-expressing NK (CD3-CD38+CD56+) cells in many diseases.
CD38+ NK cell proportions in the peripheral blood and synovial fluid are increased in patients with rheumatoid arthritis (RA), and these cells produce high levels of interferon-γ (IFN-γ) and low levels of transforming growth factor-β (TGF-β), suppressing the differentiation of CD4+ T cells to regulatory T cells (Tregs) to disrupt immune tolerance. CD38+ NK cell proportions in the peripheral blood and tumor tissues are also increased in patients with colorectal cancer (CRC).
However, CD38+ NK cells produce low levels of IFN-γ and NAD+ and high levels of TGF-β and adenosine (ADO) and can promote Treg differentiation and macrophage polarization to tumor-associated macrophages (TAMs) to interrupt immune surveillance. CD38+ NK cells were not detected in CD38-KO tumor-bearing mice, and their xenograft tumors grew slowly.
Frontiers in Immunology published a clinical update in Infectious Disease on 29 May 2026.
The item focuses on CD38+ NK cells: novel players in immunoregulation.
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