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A committed precursor to innate lymphoid cell lineages, but not classical natural killer and lymphoid tissue inducer cells, is derived from common lymphoid precursors and distinguished by high levels of expression of the transcription factor PLZF. Innate lymphoid cell precursors identified Knowledge of the developmental pathways and lineage relationships of the precursors to innate lymphocytes is important because these cells serve key protective functions in infection and homeostasis at mucosal barriers, and because of their crosstalk with epithelium and microbiota. This study identifies a committed common lymphoid-derived precursor to innate lymphoid cell (ILC) lineages. The progenitor cells, termed ILCPs (innate lymphoid cell precursors), are distinct from classical natural killer (NK) and lymphoid tissue inducer cells, thus demonstrating that similar functional programs arise independently in different lineages of innate lymphocytes. The findings also imply the presence of highly specialized innate lymphoid lineages within what was previously regarded as a broader NK-cell population. Innate lymphoid cells (ILCs) specialize in the rapid secretion of polarized sets of cytokines and chemokines to combat infection and promote tissue repair at mucosal barriers.sup.1,2,3,4,5,6,7,8,9. Their diversity and similarities with previously characterized natural killer (NK) cells and lymphoid tissue inducers (LTi) have prompted a provisional classification of all innate lymphocytes into groups 1, 2 and 3 solely on the basis of cytokine properties.sup.10, but their developmental pathways and lineage relationships remain elusive. Here we identify and characterize a novel subset of lymphoid precursors in mouse fetal liver and adult bone marrow that transiently express high amounts of PLZF, a transcription factor previously associated with NK T cell development.sup.11,12, by using lineage tracing and transfer studies. PLZF.sup.high cells were committed ILC progenitors with multiple ILC1, ILC2 and ILC3 potential at the clonal level. They excluded classical LTi and NK cells, but included a peculiar subset of NK1.1.sup.+DX5.sup.- 'NK-like' cells residing in the liver. Deletion of PLZF markedly altered the development of several ILC subsets, but not LTi or NK cells. PLZF.sup.high precursors also expressed high amounts of ID2 and GATA3, as well as TOX, a known regulator of PLZF-independent NK and LTi lineages.sup.13. These findings establish novel lineage relationships between ILC, NK and LTi cells, and identify the common precursor to ILCs, termed ILCP. They also reveal the broad, defining role of PLZF in the differentiation of innate lymphocytes., Author(s): Michael G. Constantinides [sup.1] , Benjamin D. McDonald [sup.1] , Philip A. Verhoef [sup.1] , Albert Bendelac [sup.1] Author Affiliations: (1) Department of Pathology, Committee on Immunology, The Howard [...]

The differentiation of several T- and B-cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodelling. Here we report that promyelocytic leukaemia [...]

Author(s): Jochen Mattner [1]; Kristin L. DeBord [2]; Nahed Ismail [3]; Randal D. Goff [4]; Carlos Cantu, III [5]; Dapeng Zhou [1]; Pierre Saint-Mezard [1]; Vivien Wang [1]; Ying Gao [...]

Author(s): Se-Ho Park [1]; Albert Bendelac [1] A key feature of the T lymphocytes of the adaptive immune system is their ability to detect minute concentrations of pathogen-derived peptides presented [...]

Author(s): Jochen Mattner; Kristin L. DeBord; Nahed Ismail; Randal D. Goff; Carlos Cantu, III; Dapeng Zhou; Pierre Saint-Mezard; Vivien Wang; Ying Gao; Ning Yin; Kasper Hoebe; Olaf Schneewind; David Walker; [...]