Development of peripheral lymphoid organs and natural killer cells depends on the helix–loop–helix inhibitor Id2

Abstract

Transcription factors with a basic helix-loop-helix (HLH) motif have been shown to be crucial for various cell differentiation processes during development of multicellular organisms. Id proteins inhibit the functions of these transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. Members of the Id family also promote cell proliferation, implying a role in the control of cell differentiation. Here we show that Id2 is indispensable for normal development of mice. Id2-/- mice lack lymph nodes and Peyer's patches. However, their splenic architecture is normal, exhibiting T-cell and B-cell compartments and distinct germinal centres. The cell population that produces lymphotoxins, essential factors for the development of secondary lymphoid organs, is barely detectable in the Id2-/- intestine. Furthermore, the null mutants show a greatly reduced population of natural killer (NK) cells, which is due to an intrinsic defect in NK-cell precursors. Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells.

T Regulatory Cells Control Numbers of NK Cells and CD8α+ Immature Dendritic Cells in the Lymph Node Paracortex

“…Indeed, NK precursors and NK cell development intermediates are present in human LNs and tonsils (5,6). In line with this, mice lacking LNs due to knockout of the helix-loop-helix inhibitor Id2 gene (Id2 Ϫ/Ϫ ) are deficient in NK cells but not T or B lymphocytes (7). Moreover, lymphotoxin ␣ (Lta)-deficient mice show impaired LN organogenesis and defective NK cell development (8).…”

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

“…Natural killer (NK) cells belong to the innate lymphoid cell (ILC) family, which share a dependency on the common cytokine receptor γ chain and the transcriptional repressor, inhibitor of DNA binding 2 (Id2) for their development 1, 2. These cells lack somatically rearranged antigen receptors like T‐ and B‐cell receptors, and are able to rapidly respond to microbial products, cytokine stimulation and contact with other leukocytes 3.…”

Transcriptional control of epidermal specification and differentiation

“…Overexpression of Id1 in keratinocytes leads to increased proliferative potential and compromised terminal differentiation [22,23]. A quarter of the Id2 knockout mice die neonatally, a key feature of mice with a dysfunctional epidermal permeability barrier, but these mice were not characterized for possible epidermal phenotypes [24]. Id proteins function in a dominant negative fashion to interfere with lineage-specific basic helix-loop-helix (bHLH) TFs (e.g.…”