Correlation between circulating innate lymphoid cell precursors and thymic function

The thymus has a high capacity to support the differentiation of ILCs, especially when E protein transcription factors are ablated. Whether it contributes to the homeostasis of ILC pools in tissues is not clear. Single-cell RNA sequencing analysis shows a substantial amount of ILC precursors in wild type but not athymic nude blood. The precursors express CD3 intracellularly (ic) but not on the surface. The abundance of Lin^-CD127⁺CD62L⁺icCD3ε⁺ precursors varies with age, peaking at 2-3 months. These cells can differentiate into various ILC subsets on OP9-DL1 stroma in vitro. In the lung, small intestine, and epidermis, icCD3ε⁺ cells differentiate into diverse ILC subsets in different tissue environments in steady state. Helminth infection promotes their differentiation toward functional ILC2s. Thus, the thymus appears to play a role in replenishing ILC pools in different peripheral tissues. Because thymic activity is age-dependent, this finding may help explain age-related differences in immune responses.