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Science 330 (6004): 665-669

Copyright © 2010 by the American Association for the Advancement of Science

Lineage Relationship Analysis of ROR{gamma}t+ Innate Lymphoid Cells

Shinichiro Sawa,1,2 Marie Cherrier,1,2 Matthias Lochner,1,2,3 Naoko Satoh-Takayama,4,5 Hans Jörg Fehling,6 Francina Langa,7 James P. Di Santo,4,5 Gérard Eberl1,2,*

Abstract: Lymphoid tissue–inducer (LTi) cells initiate the development of lymphoid tissues through the activation of local stromal cells in a process similar to inflammation. LTi cells express the nuclear hormone receptor ROR{gamma}t, which also directs the expression of the proinflammatory cytokine interleukin-17 in T cells. We show here that LTi cells are part of a larger family of proinflammatory ROR{gamma}t+ innate lymphoid cells (ILCs) that differentiate from distinct fetal liver ROR{gamma}t+ precursors. The fate of ROR{gamma}t+ ILCs is determined by mouse age, and after birth, favors the generation of cells involved in intestinal homeostasis and defense. Contrary to ROR{gamma}t+ T cells, however, ROR{gamma}t+ ILCs develop in the absence of microbiota. Our study indicates that ROR{gamma}t+ ILCs evolve to preempt intestinal colonization by microbial symbionts.

1 Lymphoid Tissue Development Unit, Institut Pasteur, 75724 Paris, France.
2 CNRS, URA1961, 75724 Paris, France.
3 Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany.
4 Innate Immunity Unit, Institut Pasteur, 75724 Paris, France.
5 Inserm, U668, 75724 Paris, France.
6 Institute of Immunology, University Clinics Ulm, Ulm, Germany.
7 Centre Ingénieurie Génétique Murine, Institut Pasteur, 75724 Paris, France.

* To whom correspondence should be addressed. E-mail: gerard.eberl{at}

Transcription factors controlling development and function of innate lymphoid cells.
Y. Tanriver and A. Diefenbach (2014)
Int. Immunol. 26, 119-128
   Abstract »    Full Text »    PDF »
Gata3 drives development of ROR{gamma}t+ group 3 innate lymphoid cells.
N. Serafini, R. G. J. Klein Wolterink, N. Satoh-Takayama, W. Xu, C. A. J. Vosshenrich, R. W. Hendriks, and J. P. Di Santo (2014)
J. Exp. Med. 211, 199-208
   Abstract »    Full Text »    PDF »
Taming the Beast within: Regulation of Innate Lymphoid Cell Homeostasis and Function.
W. Xu and J. P. Di Santo (2013)
J. Immunol. 191, 4489-4496
   Abstract »    Full Text »    PDF »
Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation.
M. Z. Cader and A. Kaser (2013)
Gut 62, 1653-1664
   Abstract »    Full Text »    PDF »
Human CD4+CD3- Innate-Like T Cells Provide a Source of TNF and Lymphotoxin-{alpha}{beta} and Are Elevated in Rheumatoid Arthritis.
V. Bekiaris, J. R. Sedy, M. Rossetti, R. Spreafico, S. Sharma, A. Rhode-Kurnow, B. C. Ware, N. Huang, M. G. Macauley, P. S. Norris, et al. (2013)
J. Immunol. 191, 4611-4618
   Abstract »    Full Text »    PDF »
Critical Role of p38 and GATA3 in Natural Helper Cell Function.
J.-i. Furusawa, K. Moro, Y. Motomura, K. Okamoto, J. Zhu, H. Takayanagi, M. Kubo, and S. Koyasu (2013)
J. Immunol. 191, 1818-1826
   Abstract »    Full Text »    PDF »
Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5+ and IL-13+ type 2 innate lymphoid cells.
R. G. J. Klein Wolterink, N. Serafini, M. van Nimwegen, C. A. J. Vosshenrich, M. J. W. de Bruijn, D. Fonseca Pereira, H. Veiga Fernandes, R. W. Hendriks, and J. P. Di Santo (2013)
PNAS 110, 10240-10245
   Abstract »    Full Text »    PDF »
Intestinal Lin-c-Kit+NKp46-CD4- Population Strongly Produces IL-22 upon IL-1{beta} Stimulation.
Y. Lee, Y. Kumagai, M. S. Jang, J.-H. Kim, B.-G. Yang, E.-J. Lee, Y.-M. Kim, S. Akira, and M. H. Jang (2013)
J. Immunol. 190, 5296-5305
   Abstract »    Full Text »    PDF »
Peyer's Patch Inducer Cells Play a Leading Role in the Formation of B and T Cell Zone Architecture.
R. Nakagawa, A. Togawa, T. Nagasawa, and S.-i. Nishikawa (2013)
J. Immunol. 190, 3309-3318
   Abstract »    Full Text »    PDF »
Lineage relationships of human interleukin-22-producing CD56+ ROR{gamma}t+ innate lymphoid cells and conventional natural killer cells.
Y.-O. Ahn, B. R. Blazar, J. S. Miller, and M. R. Verneris (2013)
Blood 121, 2234-2243
   Abstract »    Full Text »    PDF »
Role of the Gut Microbiota in the Development and Function of Lymphoid Cells.
N. Kamada and G. Nunez (2013)
J. Immunol. 190, 1389-1395
   Abstract »    Full Text »    PDF »
Distinct requirements for T-bet in gut innate lymphoid cells.
G. Sciume, K. Hirahara, H. Takahashi, A. Laurence, A. V. Villarino, K. L. Singleton, S. P. Spencer, C. Wilhelm, A. C. Poholek, G. Vahedi, et al. (2012)
J. Exp. Med. 209, 2331-2338
   Abstract »    Full Text »    PDF »
Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1.
M. J. Bunders, C. M. van der Loos, P. L. Klarenbeek, J. L. van Hamme, K. Boer, J. C. H. Wilde, N. de Vries, R. A. W. van Lier, N. Kootstra, S. T. Pals, et al. (2012)
Blood 120, 4383-4390
   Abstract »    Full Text »    PDF »
Inhibitors of DNA Binding Proteins Restrict T Cell Potential by Repressing Notch1 Expression in Flt3-Negative Common Lymphoid Progenitors.
A. Pereira de Sousa, C. Berthault, A. Granato, S. Dias, C. Ramond, B. L. Kee, A. Cumano, and P. Vieira (2012)
J. Immunol. 189, 3822-3830
   Abstract »    Full Text »    PDF »
Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis.
J. S. A. Perry, S. Han, Q. Xu, M. L. Herman, L. B. Kennedy, G. Csako, and B. Bielekova (2012)
Science Translational Medicine 4, 145ra106
   Abstract »    Full Text »    PDF »
Interactions Between the Microbiota and the Immune System.
L. V. Hooper, D. R. Littman, and A. J. Macpherson (2012)
Science 336, 1268-1273
   Abstract »    Full Text »    PDF »
Notch, Id2, and ROR{gamma}t sequentially orchestrate the fetal development of lymphoid tissue inducer cells.
M. Cherrier, S. Sawa, and G. Eberl (2012)
J. Exp. Med. 209, 729-740
   Abstract »    Full Text »    PDF »
Interleukin-22 Drives Endogenous Thymic Regeneration in Mice.
J. A. Dudakov, A. M. Hanash, R. R. Jenq, L. F. Young, A. Ghosh, N. V. Singer, M. L. West, O. M. Smith, A. M. Holland, J. J. Tsai, et al. (2012)
Science 336, 91-95
   Abstract »    Full Text »    PDF »
Natural Aryl Hydrocarbon Receptor Ligands Control Organogenesis of Intestinal Lymphoid Follicles.
E. A. Kiss, C. Vonarbourg, S. Kopfmann, E. Hobeika, D. Finke, C. Esser, and A. Diefenbach (2011)
Science 334, 1561-1565
   Abstract »    Full Text »    PDF »
Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection.
A. S. Rolig, J. E. Carter, and K. M. Ottemann (2011)
PNAS 108, 19749-19754
   Abstract »    Full Text »    PDF »
Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor.
E. Narni-Mancinelli, J. Chaix, A. Fenis, Y. M. Kerdiles, N. Yessaad, A. Reynders, C. Gregoire, H. Luche, S. Ugolini, E. Tomasello, et al. (2011)
PNAS 108, 18324-18329
   Abstract »    Full Text »    PDF »
Identity, regulation and in vivo function of gut NKp46+ROR{gamma}t+ and NKp46+ROR{gamma}t- lymphoid cells.
A. Reynders, N. Yessaad, T.-P. Vu Manh, M. Dalod, A. Fenis, C. Aubry, G. Nikitas, B. Escaliere, J. C. Renauld, O. Dussurget, et al. (2011)
EMBO J. 30, 2934-2947
   Abstract »    Full Text »    PDF »
Th17 Cells Induce Colitis and Promote Th1 Cell Responses through IL-17 Induction of Innate IL-12 and IL-23 Production.
T. Feng, H. Qin, L. Wang, E. N. Benveniste, C. O. Elson, and Y. Cong (2011)
J. Immunol. 186, 6313-6318
   Abstract »    Full Text »    PDF »
The Yin and Yang of Signaling in Tregs and TH17 Cells.
F. Pan, H. Fan, L. Lu, Z. Liu, and S. Jiang (2011)
Science Signaling 4, mr4
   Abstract »    Full Text »    PDF »
Innate Lymphoid Cell Relations.
M. Veldhoen and D. R. Withers (2010)
Science 330, 594-595
   Abstract »    Full Text »    PDF »

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