Figure 2.

Regulation of NK cells and ILCs by RAs. Common ILC progenitors (cILCP or also called αLP) and common helper-like ILC progenitors generate ILCs. Generation and functional maturation of innate lymphocytes are primarily regulated by cytokines and transcription factors. In addition, RAs regulate these NK cells and ILCs. RAs bidirectionally regulate NK cell functions. They induce MICA and MICB to indirectly activate NK cells but can directly suppress NK cell activation as well. While the overall effect of RAs on NK cells during various types of immune responses needs to be established, it appears that RAs function to support NK cell activity but restrain their activity in certain conditions. In general, RAs promote ILC1 and ILC3 activity, whereas they suppress ILC2 generation from ILC progenitors from the bone marrow or embryonic hematopoietic organs. RAs promote IL-22 production by ILC3 to strengthen the barrier immunity, and support IFN-γ production by ILC1. These ILC-boosting functions of RAs were observed on human ILCs as well. However, there appear to be species-specific differences in the regulation. Overall, RAs are important regulators of ILCs. The arrows indicate either positive (↑) or negative (↓) effect of RAs.

ADCC, antibody-dependent cell cytotoxicity; KIR, killer inhibitory receptor; MICA, major histocompatibility complex class I chain-related protein A; MICB, major histocompatibility complex class I chain-related protein B; RXR, retinoid X receptor; TSLP, thymic stromal lymphopoietin.