Figure 1.

Schematic model of chemoattractant receptor expression during mouse NK cell development and of transcription factors involved in NK cell commitment and maturation. Several stages of differentiation have been defined during which NK cells progressively acquire maturation markers (2–4). Three stages (I–III) corresponding to different levels of functional competence were described in mature CD49b⁺ (DX5⁺) NK cells, being CD27^highCD11b^low and CD11b^highCD27^high fully competent and a later stage of differentiation marked by the inhibitory receptor KLRG1 having reduced functional capacity. Besides mNK, iNK are found in peripheral tissues, such as liver and thymus, where they represent NK cells with tissue-specific phenotype and functions possibly arising from a BM precursor. Chemokine and S1P receptor expression is developmentally regulated and is associated to selective functions in NK cell localization and maturation in BM. For example, CX3CR1 and S1P₅ play an important and non-redundant role in mature NK cell egress from BM. Although, it is not known whether these two receptors are co-expressed by the same cell or expressed by different cell populations, prompting an investigation on how they co-operate to allow the efficient export of NK cells into circulation. Chemokine receptor expression overlaps that of several transcription factors active during NK cell development. Indeed some of these transcription factors, including T-bet and Myb were shown to directly affect chemokine and S1P receptor expression. Shown are transcription factors at the stage where they play a role in development. Asterisks identify chemoattractant receptors whose deficiency affects NK cell development. Line width is proportional to expression levels.