Human RORγt+CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells

Elisa Montaldo, Luiz Gustavo Teixeira-Alves, Timor Glatzer, Pawel Durek, Ulrik Stervbo, Wiebke Hamann, Marina Babic, Daniela Paclik, Katharina Stölzel, Jörn Gröne, Laura Lozza, Kerstin Juelke, Nadine Matzmohr, Fabrizio Loiacono, Francesca Petronelli, Nicholas David Huntington, Lorenzo Moretta, Maria Cristina Mingari, Chiara Romagnani

Research output: Contribution to journalArticle

Abstract

Group 3 innate lymphoid cells (ILC3s) are defined bythe expression of the transcription factor RORγt, which is selectively required for their development. The lineage-specified progenitors of ILC3s and their site of development after birth remain undefined. Here we identified a population of human CD34+ hematopoietic progenitor cells (HPCs) that express RORγt and share a distinct transcriptional signature with ILC3s. RORγt+CD34+ HPCs were located in tonsils and intestinal lamina propria (LP) and selectively differentiated toward ILC3s. In contrast, RORγt-CD34+ HPCs could differentiate to become either ILC3s or natural killer (NK) cells, with differentiation toward ILC3 lineage determined by stem cell factor (SCF) and aryl hydrocarbon receptor (AhR) signaling. Thus, we demonstrate that in humans RORγt+CD34+ cells are lineage-specified progenitors of IL-22+ ILC3s and propose that tonsils and intestinal LP, which are enriched both in committed precursors and mature ILC3s, might represent preferential sites of ILC3 lineage differentiation.

Original languageEnglish
Pages (from-to)988-1000
Number of pages13
JournalImmunity
Volume41
Issue number6
DOIs
Publication statusPublished - Dec 18 2014

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Cell Lineage
Hematopoietic Stem Cells
Palatine Tonsil
Lymphocytes
Mucous Membrane
Aryl Hydrocarbon Receptors
Stem Cell Factor
Natural Killer Cells
Cell Differentiation
Transcription Factors
Parturition
Population

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology
  • Medicine(all)

Cite this

Montaldo, E., Teixeira-Alves, L. G., Glatzer, T., Durek, P., Stervbo, U., Hamann, W., ... Romagnani, C. (2014). Human RORγt+CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells. Immunity, 41(6), 988-1000. https://doi.org/10.1016/j.immuni.2014.11.010

Human RORγt+CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells. / Montaldo, Elisa; Teixeira-Alves, Luiz Gustavo; Glatzer, Timor; Durek, Pawel; Stervbo, Ulrik; Hamann, Wiebke; Babic, Marina; Paclik, Daniela; Stölzel, Katharina; Gröne, Jörn; Lozza, Laura; Juelke, Kerstin; Matzmohr, Nadine; Loiacono, Fabrizio; Petronelli, Francesca; Huntington, Nicholas David; Moretta, Lorenzo; Mingari, Maria Cristina; Romagnani, Chiara.

In: Immunity, Vol. 41, No. 6, 18.12.2014, p. 988-1000.

Research output: Contribution to journalArticle

Montaldo, E, Teixeira-Alves, LG, Glatzer, T, Durek, P, Stervbo, U, Hamann, W, Babic, M, Paclik, D, Stölzel, K, Gröne, J, Lozza, L, Juelke, K, Matzmohr, N, Loiacono, F, Petronelli, F, Huntington, ND, Moretta, L, Mingari, MC & Romagnani, C 2014, 'Human RORγt+CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells', Immunity, vol. 41, no. 6, pp. 988-1000. https://doi.org/10.1016/j.immuni.2014.11.010
Montaldo E, Teixeira-Alves LG, Glatzer T, Durek P, Stervbo U, Hamann W et al. Human RORγt+CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells. Immunity. 2014 Dec 18;41(6):988-1000. https://doi.org/10.1016/j.immuni.2014.11.010
Montaldo, Elisa ; Teixeira-Alves, Luiz Gustavo ; Glatzer, Timor ; Durek, Pawel ; Stervbo, Ulrik ; Hamann, Wiebke ; Babic, Marina ; Paclik, Daniela ; Stölzel, Katharina ; Gröne, Jörn ; Lozza, Laura ; Juelke, Kerstin ; Matzmohr, Nadine ; Loiacono, Fabrizio ; Petronelli, Francesca ; Huntington, Nicholas David ; Moretta, Lorenzo ; Mingari, Maria Cristina ; Romagnani, Chiara. / Human RORγt+CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells. In: Immunity. 2014 ; Vol. 41, No. 6. pp. 988-1000.
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AU - Durek, Pawel

AU - Stervbo, Ulrik

AU - Hamann, Wiebke

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AU - Stölzel, Katharina

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AU - Matzmohr, Nadine

AU - Loiacono, Fabrizio

AU - Petronelli, Francesca

AU - Huntington, Nicholas David

AU - Moretta, Lorenzo

AU - Mingari, Maria Cristina

AU - Romagnani, Chiara

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N2 - Group 3 innate lymphoid cells (ILC3s) are defined bythe expression of the transcription factor RORγt, which is selectively required for their development. The lineage-specified progenitors of ILC3s and their site of development after birth remain undefined. Here we identified a population of human CD34+ hematopoietic progenitor cells (HPCs) that express RORγt and share a distinct transcriptional signature with ILC3s. RORγt+CD34+ HPCs were located in tonsils and intestinal lamina propria (LP) and selectively differentiated toward ILC3s. In contrast, RORγt-CD34+ HPCs could differentiate to become either ILC3s or natural killer (NK) cells, with differentiation toward ILC3 lineage determined by stem cell factor (SCF) and aryl hydrocarbon receptor (AhR) signaling. Thus, we demonstrate that in humans RORγt+CD34+ cells are lineage-specified progenitors of IL-22+ ILC3s and propose that tonsils and intestinal LP, which are enriched both in committed precursors and mature ILC3s, might represent preferential sites of ILC3 lineage differentiation.

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