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Cell. 2014 Apr 10;157(2):340-356. doi: 10.1016/j.cell.2014.03.030.

Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages.

Author information

1
Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany.
2
Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany.
3
Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
4
Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Max-Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
5
Genomics Lab, Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.
6
Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
7
Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
8
Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany; BIOSS, Centre of Biological Signalling Studies, Albert Ludwigs University Freiburg, Schänzlestrasse 18, 79104 Freiburg, Germany.
9
Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohrgasse 7, 1020 Vienna, Austria.
10
Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany.
11
Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany. Electronic address: diefenbach@uni-mainz.de.

Abstract

Innate lymphoid cells (ILCs) are a recently recognized group of lymphocytes that have important functions in protecting epithelial barriers against infections and in maintaining organ homeostasis. ILCs have been categorized into three distinct groups, transcriptional circuitry and effector functions of which strikingly resemble the various T helper cell subsets. Here, we identify a common, Id2-expressing progenitor to all interleukin 7 receptor-expressing, "helper-like" ILC lineages, the CHILP. Interestingly, the CHILP differentiated into ILC2 and ILC3 lineages, but not into conventional natural killer (cNK) cells that have been considered an ILC1 subset. Instead, the CHILP gave rise to a peculiar NKp46(+) IL-7Rα(+) ILC lineage that required T-bet for specification and was distinct of cNK cells or other ILC lineages. Such ILC1s coproduced high levels of IFN-γ and TNF and protected against infections with the intracellular parasite Toxoplasma gondii. Our data significantly advance our understanding of ILC differentiation and presents evidence for a new ILC lineage that protects barrier surfaces against intracellular infections.

PMID:
24725403
DOI:
10.1016/j.cell.2014.03.030
[Indexed for MEDLINE]
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