Blood Journal
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Expression of BMPRIA on human thymic NK cell precursors: role of BMP signaling in intrathymic NK cell development

  1. Laura Hidalgo1,
  2. Víctor G. Martínez1,
  3. Jaris Valencia1,
  4. Carmen Hernández-López1,
  5. Miriam N. Vázquez1,
  6. José R. Nuñez2,
  7. Agustín G. Zapata3,
  8. Rosa Sacedón1,
  9. Alberto Varas1,*, and
  10. Angeles Vicente1,*
  1. 1Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain; and
  2. 2Transplant Coordination Unit, Hospital Clínico San Carlos, Faculty of Medicine, Complutense University, Madrid, Spain; and
  3. 3Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain

Abstract

The bone morphogenetic protein (BMP) signaling pathway regulates survival, proliferation, and differentiation of several cell types in multiple tissues, including the thymus. Previous reports have shown that BMP signaling negatively regulates T-cell development. Here, we study the subpopulation of early human intrathymic progenitors expressing the type IA BMP receptor (BMPRIA) and provide evidence that CD34+CD1aBMPRIA+ precursor cells mostly express surface cell markers and transcription factors typically associated with NK cell lineage. These CD34+ cells mostly differentiate into functional CD56+ natural killer (NK) cells when they are cocultured with thymic stromal cells in chimeric human-mouse fetal thymic organ cultures and also in the presence of SCF and IL-15. Moreover, autocrine BMP signaling can promote the differentiation of thymic NK cells by regulating the expression of key transcription factors required for NK cell lineage (eg, Id3 and Nfil3) as well as one of the components of IL-15 receptor, CD122. Subsequently, the resulting population of IL-15–responsive NK cell precursors can be expanded by IL-15, whose action is mediated by BMP signaling during the last steps of thymic NK cell differentiation. Our results strongly suggest that BMPRIA expression identifies human thymic NK cell precursors and that BMP signaling is relevant for NK cell differentiation in the human thymus.

  • Submitted July 29, 2011.
  • Accepted December 16, 2011.
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