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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2625-2632
HEMATOPOIESIS
Differential requirement for the transcription factor PU.1 in the
generation of natural killer cells versus B and T cells
Francesco Colucci,
Sandrine
I. Samson,
Rodney P. DeKoter,
Olivier Lantz,
Harinder Singh, and
James P. Di Santo
From the Laboratory for Cytokines and Lymphoid
Development, Pasteur Institute, Paris, France; Howard Hughes Medical
Institute, The University of Chicago, Chicago, Illinois; and Institut
National de la Santé et de la Recherche Médicale U25,
Necker Hospital, Paris, France.
PU.1 is a member of the Ets family of transcription factors
required for the development of various lymphoid and myeloid cell lineages, but its role in natural killer (NK) cell development is not
known. The study shows that PU.1 is expressed in NK cells and that, on
cell transfer into alymphoid Rag2/ c /
mice, hematopoietic progenitors of PU.1/
fetal liver cells could generate functional NK cells but not B or T
cells. Nevertheless, the numbers of bone marrow NK cell precursors and
splenic mature NK cells were reduced compared to controls. Moreover,
PU.1/ NK cells displayed reduced expression
of the receptors for stem cell factor and interleukin (IL)-7,
suggesting a nonredundant role for PU.1 in regulating the expression of
these cytokine receptor genes during NK cell development.
PU.1/ NK cells also showed defective
expression of inhibitory and activating members of the Ly49 family and
failed to proliferate in response to IL-2 and IL-12. Thus, despite the
less stringent requirement for PU.1 in NK cell development compared to
B and T cells, PU.1 regulates NK cell differentiation and homeostasis.
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