Journal
ISCIENCE
Volume 25, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.103732
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Funding
- NIH [1R01AI126851, 1S10OD028479-01]
- Presbyterian Health Foundation
- Oklahoma Center for the Advancement of Science and Technology [HR16-085]
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The thymus plays a role in maintaining the homeostasis of ILC pools in tissues, especially in the absence of E protein transcription factors. ILC precursors can differentiate into various subsets in vitro, and in steady state, icCD3 epsilon(+) cells differentiate into diverse ILC subsets in different tissue environments. Helminth infection promotes their differentiation into functional ILC2s. This finding may help explain age-related differences in immune responses, as thymic activity is age-dependent.
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(+)icCD3 epsilon(+) precursors varies with age, peaking at 2-3 months. These cells can differentiate into various ILC subsets on OP9DL1 stroma in vitro. In the lung, small intestine, and epidermis, icCD3 epsilon(+) 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.
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