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Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs


Nussbaum, Kathrin; Burkhard, Sara H; Ohs, Isabel; Mair, Florian; Klose, Christoph S N; Arnold, Sebastian J; Diefenbach, Andreas; Tugues, Sonia; Becher, Burkhard (2017). Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs. Journal of Experimental Medicine, 214(8):2331-2347.

Abstract

Innate lymphoid cells (ILCs) have been classified into "functional subsets" according to their transcription factor and cytokine profiles. Although cytokines, such as IL-12 and IL-23, have been shown to shape plasticity of ILCs, little is known about how the tissue microenvironment influences the plasticity, phenotype, and function of these cells. Here, we show clearly demarcated tissue specifications of Rorc-dependent ILCs across lymphoid and nonlymphoid organs. Although intestinal Rorc fate map-positive (Rorc(fm+)) ILCs show a clear ILC3 phenotype, lymphoid tissue-derived Rorc(fm+) ILCs acquire an natural killer (NK) cell/ILC1-like phenotype. By adoptively transferring Rorc(fm+) ILCs into recipient mice, we show that ILCs distribute among various organs and phenotypically adapt to the tissue environment they invade. When investigating their functional properties, we found that only lymphoid-tissue resident Rorc(fm+) ILCs can suppress tumor growth, whereas intestinal Rorc(fm-) ILC1s or NK cells fail to inhibit tumor progression. We thus propose that the tissue microenvironment, combined with ontogeny, provides the specific function, whereas the phenotype is insufficient to predict the functional properties of ILCs.

Abstract

Innate lymphoid cells (ILCs) have been classified into "functional subsets" according to their transcription factor and cytokine profiles. Although cytokines, such as IL-12 and IL-23, have been shown to shape plasticity of ILCs, little is known about how the tissue microenvironment influences the plasticity, phenotype, and function of these cells. Here, we show clearly demarcated tissue specifications of Rorc-dependent ILCs across lymphoid and nonlymphoid organs. Although intestinal Rorc fate map-positive (Rorc(fm+)) ILCs show a clear ILC3 phenotype, lymphoid tissue-derived Rorc(fm+) ILCs acquire an natural killer (NK) cell/ILC1-like phenotype. By adoptively transferring Rorc(fm+) ILCs into recipient mice, we show that ILCs distribute among various organs and phenotypically adapt to the tissue environment they invade. When investigating their functional properties, we found that only lymphoid-tissue resident Rorc(fm+) ILCs can suppress tumor growth, whereas intestinal Rorc(fm-) ILC1s or NK cells fail to inhibit tumor progression. We thus propose that the tissue microenvironment, combined with ontogeny, provides the specific function, whereas the phenotype is insufficient to predict the functional properties of ILCs.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:7 August 2017
Deposited On:05 Oct 2017 13:30
Last Modified:05 Oct 2017 13:31
Publisher:Rockefeller University Press
ISSN:0022-1007
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1084/jem.20162031
PubMed ID:28698286

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