Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 6, Pages 2402-2407Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1016257108
Keywords
natural killer cell development; natural killer receptor; immunity in pregnancy
Categories
Funding
- Fondazione Italiana per la Ricerca sul Cancro
- Associazione Italiana per la Ricerca sul Cancro
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [20077NFBH8_005]
- Fondo Investimenti Ricerca di Base (FIRB)
- Progetti Ricerca Interesse Nazionale (PRIN) [RBLA039LSF-001/003, 2008PTB3HC_005]
- Ministero della Salute
- Ministero della Salute Progetto Strategico [RFPS-2007-4-633146]
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Natural killer (NK) cells are the main lymphoid population in the maternal decidua during the first trimester of pregnancy. Decidual NK (dNK) cells display a unique functional profile and play a key role in promoting tissue remodeling, neoangiogenesis, and immune modulation. However, little information exists on their origin and development. Here we discovered CD34(+) hematopoietic precursors in human decidua (dCD34(+)). We show that dCD34(+) cells differ from cord blood-or peripheral blood-derived CD34(+) precursors. The expression of IL-15/IL-2 receptor common beta-chain (CD122), IL-7 receptor alpha-chain (CD127), and mRNA for E4BP4 and ID2 transcription factors suggested that dCD34(+) cells are committed to the NK cell lineage. Moreover, they could undergo in vitro differentiation into functional (i.e., IL-8- and IL-22-producing) CD56(bright)CD16(-)KIR(+/-) NK cells in the presence of growth factors or even upon coculture with decidual stromal cells. Their NK cell commitment was further supported by the failure to undergo myeloid differentiation in the presence of GM-CSF. Our findings strongly suggest that decidual NK cells may directly derive from CD34(+) cell precursors present in the decidua upon specific cellular interactions with components of the decidual microenvironment.
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