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Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation

Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissue-inducer (LTi)-like and NKp46(+) subsets. Both depend on RORγt and aryl hydrocarbon receptor, but NKp46(+)ILC3s also require Notch and T-bet for their development and are transcriptionally distinct. The extent to w...

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Autores principales: Song, Christina, Lee, Jacob S., Gilfillan, Susan, Robinette, Michelle L., Newberry, Rodney D., Stappenbeck, Thaddeus S., Mack, Matthias, Cella, Marina, Colonna, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612098/
https://www.ncbi.nlm.nih.gov/pubmed/26458769
http://dx.doi.org/10.1084/jem.20151403
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author Song, Christina
Lee, Jacob S.
Gilfillan, Susan
Robinette, Michelle L.
Newberry, Rodney D.
Stappenbeck, Thaddeus S.
Mack, Matthias
Cella, Marina
Colonna, Marco
author_facet Song, Christina
Lee, Jacob S.
Gilfillan, Susan
Robinette, Michelle L.
Newberry, Rodney D.
Stappenbeck, Thaddeus S.
Mack, Matthias
Cella, Marina
Colonna, Marco
author_sort Song, Christina
collection PubMed
description Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissue-inducer (LTi)-like and NKp46(+) subsets. Both depend on RORγt and aryl hydrocarbon receptor, but NKp46(+)ILC3s also require Notch and T-bet for their development and are transcriptionally distinct. The extent to which these subsets have unique functions, especially in the context of T cell– and B cell–sufficient mice, remains largely unclear. To investigate the specific function of NKp46(+)ILC3s among other ILC3 subsets and T cells, we generated mice selectively lacking NKp46(+)ILC3s or all ILC3s and crossed them to T cell–deficient mice, thus maintaining B cells in all mice. In mice lacking T cells, NKp46(+)ILC3s were sufficient to promote inflammatory monocyte accumulation in the anti-CD40 innate colitis model through marked production of GM-CSF. In T cell–competent mice, lack of NKp46(+)ILCs had no impact on control of intestinal C. rodentium infection, whereas lack of all ILC3s partially impaired bacterial control. Thus, NKp46(+)ILC3s have a unique capacity to promote inflammation through GM-CSF–induced accumulation of inflammatory monocytes, but are superseded by LTi-like ILC3s and T cells in controlling intestinal bacterial infection.
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spelling pubmed-46120982016-04-19 Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation Song, Christina Lee, Jacob S. Gilfillan, Susan Robinette, Michelle L. Newberry, Rodney D. Stappenbeck, Thaddeus S. Mack, Matthias Cella, Marina Colonna, Marco J Exp Med Article Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissue-inducer (LTi)-like and NKp46(+) subsets. Both depend on RORγt and aryl hydrocarbon receptor, but NKp46(+)ILC3s also require Notch and T-bet for their development and are transcriptionally distinct. The extent to which these subsets have unique functions, especially in the context of T cell– and B cell–sufficient mice, remains largely unclear. To investigate the specific function of NKp46(+)ILC3s among other ILC3 subsets and T cells, we generated mice selectively lacking NKp46(+)ILC3s or all ILC3s and crossed them to T cell–deficient mice, thus maintaining B cells in all mice. In mice lacking T cells, NKp46(+)ILC3s were sufficient to promote inflammatory monocyte accumulation in the anti-CD40 innate colitis model through marked production of GM-CSF. In T cell–competent mice, lack of NKp46(+)ILCs had no impact on control of intestinal C. rodentium infection, whereas lack of all ILC3s partially impaired bacterial control. Thus, NKp46(+)ILC3s have a unique capacity to promote inflammation through GM-CSF–induced accumulation of inflammatory monocytes, but are superseded by LTi-like ILC3s and T cells in controlling intestinal bacterial infection. The Rockefeller University Press 2015-10-19 /pmc/articles/PMC4612098/ /pubmed/26458769 http://dx.doi.org/10.1084/jem.20151403 Text en © 2015 Song et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Song, Christina
Lee, Jacob S.
Gilfillan, Susan
Robinette, Michelle L.
Newberry, Rodney D.
Stappenbeck, Thaddeus S.
Mack, Matthias
Cella, Marina
Colonna, Marco
Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation
title Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation
title_full Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation
title_fullStr Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation
title_full_unstemmed Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation
title_short Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation
title_sort unique and redundant functions of nkp46(+) ilc3s in models of intestinal inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612098/
https://www.ncbi.nlm.nih.gov/pubmed/26458769
http://dx.doi.org/10.1084/jem.20151403
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