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PMID:17452521

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Citation

Boos, MD, Yokota, Y, Eberl, G and Kee, BL (2007) Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J. Exp. Med. 204:1119-30

Abstract

The Id2 transcriptional repressor is essential for development of natural killer (NK) cells, lymphoid tissue-inducing (LTi) cells, and secondary lymphoid tissues. Id2 was proposed to regulate NK and LTi lineage specification from multipotent progenitors through suppression of E proteins. We report that NK cell progenitors are not reduced in the bone marrow (BM) of Id2(-/-) mice, demonstrating that Id2 is not essential for NK lineage specification. Rather, Id2 is required for development of mature (m) NK cells. We define the mechanism by which Id2 functions by showing that a reduction in E protein activity, through deletion of E2A, overcomes the need for Id2 in development of BM mNK cells, LTi cells, and secondary lymphoid tissues. However, mNK cells are not restored in the blood or spleen of Id2(-/-)E2A(-/-) mice, suggesting a role for Id2 in suppression of alternative E proteins after maturation. Interestingly, the few splenic mNK cells in Id2(-/-) and Id2(-/-)E2A(-/-) mice have characteristics of thymus-derived NK cells, which develop in the absence of Id2, implying a differential requirement for Id2 in BM and thymic mNK development. Our findings redefine the essential functions of Id2 in lymphoid development and provide insight into the dynamic regulation of E and Id proteins during this process.

Links

PubMed PMC2118569 Online version:10.1084/jem.20061959

Keywords

Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/immunology; Cell Differentiation/immunology; Cell Lineage/immunology; DNA Primers; Flow Cytometry; Gene Expression Regulation/immunology; Genotype; Inhibitor of Differentiation Protein 2/genetics; Inhibitor of Differentiation Protein 2/immunology; Killer Cells, Natural/immunology; Lymphoid Tissue/immunology; Mice; Mice, Knockout; Microscopy, Fluorescence; Polymerase Chain Reaction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TFE2

acts_upstream_of_or_within

GO:0001779: natural killer cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96397

P

  • occurs_in:(EMAPA:32760)
  • results_in_acquisition_of_features_of:(CL:0000824)

Seeded From UniProt

complete

MOUSE:TFE2

acts_upstream_of_or_within

GO:0048541: Peyer's patch development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98510

P

  • results_in_development_of:(EMAPA:19028)

Seeded From UniProt

complete

MOUSE:TFE2

acts_upstream_of_or_within

GO:0048468: cell development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96397

P

  • occurs_in:(CL:0000824)
  • occurs_in:(EMAPA:32760)

Seeded From UniProt

complete

MOUSE:ID2

acts_upstream_of_or_within

GO:0001779: natural killer cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384134

P

  • occurs_in:(EMAPA:32760)
  • results_in_acquisition_of_features_of:(CL:0000824)|occurs_in(EMAPA:18767)
  • results_in_acquisition_of_features_of:(CL:0000824)

Seeded From UniProt

complete

MOUSE:ID2

acts_upstream_of_or_within

GO:0001779: natural killer cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98510

P

  • occurs_in:(EMAPA:32760)
  • results_in_acquisition_of_features_of:(CL:0000824)

Seeded From UniProt

complete

MOUSE:ID2

acts_upstream_of_or_within

GO:0048541: Peyer's patch development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98510

P

  • results_in_development_of:(EMAPA:19028)

Seeded From UniProt

complete

MOUSE:ID2

acts_upstream_of_or_within

GO:0048469: cell maturation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384134

P

  • occurs_in:(EMAPA:32760)
  • results_in_maturation_of:(CL:0000824)|occurs_in(EMAPA:18767)
  • results_in_maturation_of:(CL:0000824)

Seeded From UniProt

complete

MOUSE:ID2

acts_upstream_of_or_within

GO:0048468: cell development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98510

P

  • occurs_in:(CL:0000824)
  • occurs_in:(EMAPA:32760)

Seeded From UniProt

complete


See also

References

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