Abstract
Members of the innate lymphoid cell (ILC) family have been implicated in the development of thymic microenvironments and the recovery of this architecture after damage. However, a detailed characterization of this family in the thymus is lacking. To better understand the thymic ILC compartment, we have utilized multiple in vivo models including the fate mapping of inhibitor of DNA binding‐2 (Id2) expression and the use of Id2 reporter mice. Our data demonstrate that ILCs are more prominent immediately after birth, but were rapidly diluted as the T‐cell development program increased. As observed in the embryonic thymus, CCR6+NKp46− lymphoid tissue inducer (LTi) cells were the main ILC3 population present, but numbers of these cells swiftly declined in the neonate and ILC3 were barely detectable in adult thymus. This loss of ILC3 means ILC2 are the dominant ILC population in the thymus. Thymic ILC2 were able to produce IL‐5 and IL‐13, were located within the medulla, and did not result from ILC3 plasticity. Furthermore, in WT mice, thymic ILC2 express little RANKL (receptor activator of nuclear factor kappa‐B ligand) arguing that functionally, these cells provide different signals to LTi cells in the thymus. Collectively, these data reveal a dynamic switch in the ILC populations of the thymus during neonatal development.
Highlights
Innate lymphoid cells (ILC) have been described in many tissues [1, 2] and it seems likely that this family of cells is present essentially throughout the body
Building on the earlier observation that lymphoid tissue inducer (LTi) cells populate the embryonic thymus and orchestrate medullary thymic epithelial cells (mTEC) maturation through RANK:RANKL interactions, we demonstrate that after birth, LTi cells decline during neonatal development while ILC2 increase in number and become the main ILC population present within the thymus
We provide evidence that thymic ILC2 are able to produce the signature cytokines IL-5 and IL-13 and reside in the medulla where they may compete for an environmental niche with ILC3
Summary
An alternative approach administering tamoxifen for a longer period of time via the diet enabled an increased proportion of ILC to be fate mapped, the data was comparable in terms of the ILC subsets identified within the thymus (Supporting Information Fig. 3). These experiments reveal that fate mapping Id2 expression does enhance our ability to identify ILC and within the adult thymus, the majority of ILC are not ILC3, but rather GATA-3+ ILC2. ILC2 can express RANKL when the thymic microenvironment is perturbed
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