Dynamic changes in intrathymic ILC populations during murine neonatal development

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.

ILC2: at home in the thymus

“…In this issue of the European Journal of Immunology , Jones and co‐workers have used both conventional and genetic methods to specifically identify ILC family members residing in the murine fetal and post‐natal thymus. In line with the importance of ILC3 for fetal thymic development, ILC3 are the major thymic ILC subset before birth.…”

“…The current study by Jones at al. is a textbook example of rigorous ILC research, relying on a combinatorial approach of conventional labeling techniques and genetic models to unequivocally identify and study distinct ILC subsets in the thymus. Taking advantage of the fetal thymic organ culture model that has been extensively used to study thymic development, the authors succeeded to analyze ILC subsets from the embryonic thymic lobes.…”

“…B). In addition to ILC2 and ILC3, a small but distinct population of thymic ILC1 is also present postnatally .…”

“…Taking advantage of the expression of Id2 during ILC development, and using Id2 and Rorγt‐based lineage tracing models and direct Id2 reporter mice, Jones et al. convincingly validated the ILC identity of the thymic cells. The inverse correlation between the increase in ILC2 numbers and the decrease in ILC3 numbers raised the possibility that thymic ILC3 might convert to ILC2 after birth.…”

“…To address this, Jones et al. made use of Rorγt‐fate map mice to lineage trace cells that had expressed this ILC3‐defining transcription factor (ex‐ILC3). Analysis of ILC marked by the Rorγt reporter revealed that in comparison to the lymph nodes, the thymus only contained a small population of ILC that had previously expressed Rorγt.…”