TY - JOUR
T1 - Natural killer-cell differentiation by myeloid progenitors
AU - Grzywacz, Bartosz
AU - Kataria, Nandini
AU - Kataria, Niketa
AU - Blazar, Bruce R.
AU - Miller, Jeffrey S.
AU - Verneris, Michael R.
PY - 2011/3/31
Y1 - 2011/3/31
N2 - Because lymphoid progenitors can give rise to natural killer (NK) cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that rare human CD34+ hematopoietic progenitors develop into NK cells in vitro in the presence of cytokines (interleukin-7, interleukin-15, stem cell factor, and fms-like tyrosine kinase-3 ligand). Adding hydrocortisone and stromal cells greatly increases the frequency of progenitor cells that give rise to NK cells through the recruitment of myeloid precursors, including common myeloid progenitors and granulocytic-monocytic precursors to the NK-cell lineage. WNT signaling was involved in this effect. Cells at more advanced stages of myeloid differentiation (with increasing expression of CD13 and macrophage colony-stimulating factor receptor [M-CSFR]) could also differentiate into NK cells in the presence of cytokines, stroma, and hydrocortisone. NK cells derived from myeloid precursors (CD56-CD117+M- CSFR+) showed more expression of killer immunoglobulin-like receptors, a fraction of killer immunoglobulin-like receptor-positive-expressing cells that lacked NKG2A, a higher cytotoxicity compared with CD56 -CD117+M-CSFR- precursor-derived NK cells and thus resemble the CD56dim subset of NK cells. Collectively, these studies show that NK cells can be derived from the myeloid lineage.
AB - Because lymphoid progenitors can give rise to natural killer (NK) cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that rare human CD34+ hematopoietic progenitors develop into NK cells in vitro in the presence of cytokines (interleukin-7, interleukin-15, stem cell factor, and fms-like tyrosine kinase-3 ligand). Adding hydrocortisone and stromal cells greatly increases the frequency of progenitor cells that give rise to NK cells through the recruitment of myeloid precursors, including common myeloid progenitors and granulocytic-monocytic precursors to the NK-cell lineage. WNT signaling was involved in this effect. Cells at more advanced stages of myeloid differentiation (with increasing expression of CD13 and macrophage colony-stimulating factor receptor [M-CSFR]) could also differentiate into NK cells in the presence of cytokines, stroma, and hydrocortisone. NK cells derived from myeloid precursors (CD56-CD117+M- CSFR+) showed more expression of killer immunoglobulin-like receptors, a fraction of killer immunoglobulin-like receptor-positive-expressing cells that lacked NKG2A, a higher cytotoxicity compared with CD56 -CD117+M-CSFR- precursor-derived NK cells and thus resemble the CD56dim subset of NK cells. Collectively, these studies show that NK cells can be derived from the myeloid lineage.
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U2 - 10.1182/blood-2010-04-281394
DO - 10.1182/blood-2010-04-281394
M3 - Article
C2 - 21173117
AN - SCOPUS:79953716796
SN - 0006-4971
VL - 117
SP - 3548
EP - 3558
JO - Blood
JF - Blood
IS - 13
ER -