Distal-less homeobox transcription factors regulate development and maturation of natural killer cells

John B. Sunwoo, Sung Jin Kim, Liping Yang, Tina Naik, Darryl A. Higuchi, John L. Rubenstein, Wayne M. Yokoyama

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Natural killer (NK) cells constitute a subpopulation of lymphocytes that develop from precursors in the bone marrow (BM), but the transcriptional regulation of their development and maturation is only beginning to be understood, in part due to their relatively rare abundance, especially of developmental subsets. Using a mouse model in which NK cells are arrested at an immature stage of development, and a gene expression profiling approach, we uncovered transient normal NK cell expression of a homeobox transcription factor (TF) family, called Distal-less (Dlx), which had been primarily implicated in murine CNS, craniofacial, limb, and skin development. Our studies demonstrate that Dlx1, Dlx2, and Dlx3 are transiently expressed in immature Mac-1 lo NK cells within the BM, with Dlx3 being the predominantly expressed member. These genes are expressed in a temporally regulated pattern with overlapping waves of expression, and they display functional redundancy. Expression is extinguished in fully mature splenic NK cells, and persistent expression of Dlx genes leads to functionally immature NK cells arrested at the Mac-1lo stage. Whereas conventional splenic NK cells develop but are arrested at an immature stage, there appears to be a complete failure to develop CD127+ thymic NK cells when Dlx genes are persistently expressed.Wealso observed that T and B cells fail to develop in the context of persistent Dlx1 expression. Thus, these studies indicate that Dlx TFs play a functional role in lymphocyte development.

Original languageEnglish (US)
Pages (from-to)10877-10882
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number31
DOIs
StatePublished - Aug 5 2008
Externally publishedYes

Fingerprint

Homeobox Genes
Natural Killer Cells
Transcription Factors
Bone Marrow
Lymphocyte Subsets
Gene Expression Profiling
Genes
B-Lymphocytes
Extremities
Lymphocytes
T-Lymphocytes
Gene Expression
Skin

Keywords

  • Dlx
  • Gene expression
  • Lymphocyte
  • NK

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Distal-less homeobox transcription factors regulate development and maturation of natural killer cells. / Sunwoo, John B.; Kim, Sung Jin; Yang, Liping; Naik, Tina; Higuchi, Darryl A.; Rubenstein, John L.; Yokoyama, Wayne M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 31, 05.08.2008, p. 10877-10882.

Research output: Contribution to journalArticle

Sunwoo, John B. ; Kim, Sung Jin ; Yang, Liping ; Naik, Tina ; Higuchi, Darryl A. ; Rubenstein, John L. ; Yokoyama, Wayne M. / Distal-less homeobox transcription factors regulate development and maturation of natural killer cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 31. pp. 10877-10882.
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