Abstract
Innate lymphoid cells (ILCs) have emerged as a key cell type involved in surveillance and maintenance of mucosal tissues. Mouse ILCs rely on the transcriptional regulator Inhibitor of DNA-binding protein 2 (Id2) for their development. Here, we show that Id2 also drives development of human ILC because forced expression of Id2 in human thymic progenitors blocked T cell commitment, upregulated CD161 and promyelocytic leukemia zinc finger (PLZF), and maintained CD127 expression, markers that are characteristic for human ILCs. Surprisingly CD5 was also expressed on these in vitro generated ILCs. This was not an in vitro artifact because CD5 was also found on ex vivo isolated ILCs from thymus and from umbilical cord blood. CD5 was also expressed on small proportions of ILC2 and ILC3. CD5+ ILCs were functionally immature, but could further differentiate into mature CD5− cytokine-secreting ILCs. Our data show that Id2 governs human ILC development from thymic progenitor cells toward immature CD5+ ILCs.
Highlights
Innate lymphoid cells (ILCs) belong to a novel lymphoid cell subfamily
Our data show that expression of Inhibitor of DNA-binding protein 2 (Id2) in human progenitor cells favors development of ILCs while inhibiting T cell and plasmacytoid dendritic cells (pDC) development [10, 11, 14, 15, 17]
As CD5 was described to be a marker that distinguishes T cells from ILCs [35] it was unexpected to observe that under conditions in which TCR gene rearrangements and T cell development is blocked, CD5+ ILCs are generated. These CD5+ ILCs cannot be T cells that have downregulated the expression of TCR, because Id2 prevents TCR gene rearrangements [10]
Summary
Innate lymphoid cells (ILCs) belong to a novel lymphoid cell subfamily. ILCs can be found throughout the body, enriched in mucosal tissues and secondary lymphoid structures where they have been implicated as important regulators of mucosal homeostasis, host–microbiota interactions, initiation of protective immunity, inflammation, and tissue repair [1,2,3]. It has been suggested that human ILC development can occur in bone marrow, and in secondary lymphoid tissues and the intestinal lamina propria [5, 6]. ILC have been found in the thymus which might imply that ILC develop in the thymus. This notion is supported by the observation in mouse and human that the thymus contains bipotential T/NK progenitors
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