Differential expression of disparate transcription factor regime holds the key for NK cell development and function modulation

Natural killer (NK) cells are involved in providing immunity against autoimmune diseases and perpetuation of a successful pregnancy in addition to protecting us from viral infections and providing tumor immunity. NK cells are present in various organs such as spleen, blood, lymph nodes, skin, liver and uterus and differential expression of transcription factors in divergent subsets of NK cells lead to differences in their cytotoxicity and cytokine profile. Tissue-specific expression and regulation of the TFs involved, has a profound effect on the cytokine profile and surface markers on NK cells, thus impacting NK cell function. Nfil-3, Id-2, Ets-1, GATA-3, and Eomes are TFs varying in abundance in peripheral NK (pNK) and uterine NK cells (uNK), which further highlights the functional variations in the two subsets of NK cells. GATA-3 mediated regulation of IFN-γ production, NK cell maturation, protection against pathogens, and regulation of expression of inhibitory NK cell receptor (NKG2A), exemplifies a potential mechanism for immune-modulation, involving NK cells. This review highlights the differences in the regulation of TFs in pNK and uNK cells, which can be crucial for development of novel immune-therapeutics.