This CD16-induced expression of cytokine mRNA in NK cells is mediated by the nuclear factor of activated T cells (NFATp), a cyclosporin A (CsA)-sensitive factor that regulates the transcription of various cytokines. The upregulated expression of specific cytokine genes occurs via a CsA-sensitive and calcium-dependent mechanism. The crystal structures of FcεRIα, FcγRIIa, FcγRIIb and FcγRIII have been experimentally determined. These structures revealed a conserved immunoglobulin-like (Ig-like) structure. In addition, the structures demonstrated a common feature in all known Ig superfamily Fc receptors: the acute hinge angle between the N- and C-terminal Ig domains. Specifically, the structure of CD16 (FcγRIIIb) consists of two immunoglobulin-like domains, with an interdomain hinge angle of around 50°. The receptor's Fc binding region also carries a net positive charge, which complements the negatively-charged receptor binding regions on Fc. CD16 plays a significant role in early activation of natural killer (NK) cells following vaccination. In addition, CD16 downregulation represents a possible way to moderate NK cell responses and maintain immune homeostasis in both T cell and antibody-dependent signaling pathways. In a normal, healthy individual, cross-linking of CD16 (FcγRIII) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) in NK cells. However, this pathway can also be targeted in cancerous or diseased cells by immunotherapy. After influenza vaccination, CD16 downregulation was associated with significant upregulation of influenza-specific plasma antibodies, and positively correlated with degranulation of NK cells. CD16 is often used as an additional marker to reliably identify different subsets of human immune cells. Several other CD molecules, such as CD11b and CD33, are traditionally used as markers for human myeloid-derived suppressor cells (MDSCs). However, since these markers are also expressed on NK cells and all other cells derived from myelocytes, other markers are required, such as CD14 and CD15. Neutrophils are found to be CD14low and CD15high, whereas monocytes are CD14high and CD15low. While these two markers are sufficient to differentiate between neutrophils and monocytes, eosinophils have a similar CD15 expression to neutrophils.