CCR7 defines a precursor for murine iNKT cells in thymus and periphery

The precise steps of iNKT subset differentiation in the thymus and periphery have been controversial. We demonstrate here that the small proportion of thymic iNKT and mucosal associated invariant T cells that express CCR7 represent a multi-potent progenitor pool that gives rise to effector subsets w...

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Main Authors: Haiguang Wang, Kristin A Hogquist
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-08-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/34793
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author Haiguang Wang
Kristin A Hogquist
author_facet Haiguang Wang
Kristin A Hogquist
author_sort Haiguang Wang
collection DOAJ
description The precise steps of iNKT subset differentiation in the thymus and periphery have been controversial. We demonstrate here that the small proportion of thymic iNKT and mucosal associated invariant T cells that express CCR7 represent a multi-potent progenitor pool that gives rise to effector subsets within the thymus. Using intra-thymic labeling, we also showed that CCR7+ iNKT cells emigrate from the thymus in a Klf2 dependent manner, and undergo further maturation after reaching the periphery. Ccr7 deficiency impaired differentiation of iNKT effector subsets and localization to the medulla. Parabiosis and intra-thymic transfer showed that thymic NKT1 and NKT17 were resident—they were not derived from and did not contribute to the peripheral pool. Finally, each thymic iNKT effector subset produces distinct factors that influence T cell development. Our findings demonstrate how the thymus is both a source of iNKT progenitors and a unique site of tissue dependent effector cell differentiation.
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spelling doaj.art-f6f915ad4bed44dc823d9bf99ef843072022-12-22T02:03:14ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.34793CCR7 defines a precursor for murine iNKT cells in thymus and peripheryHaiguang Wang0https://orcid.org/0000-0001-5403-9179Kristin A Hogquist1https://orcid.org/0000-0001-9963-5687The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, United StatesThe Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, United StatesThe precise steps of iNKT subset differentiation in the thymus and periphery have been controversial. We demonstrate here that the small proportion of thymic iNKT and mucosal associated invariant T cells that express CCR7 represent a multi-potent progenitor pool that gives rise to effector subsets within the thymus. Using intra-thymic labeling, we also showed that CCR7+ iNKT cells emigrate from the thymus in a Klf2 dependent manner, and undergo further maturation after reaching the periphery. Ccr7 deficiency impaired differentiation of iNKT effector subsets and localization to the medulla. Parabiosis and intra-thymic transfer showed that thymic NKT1 and NKT17 were resident—they were not derived from and did not contribute to the peripheral pool. Finally, each thymic iNKT effector subset produces distinct factors that influence T cell development. Our findings demonstrate how the thymus is both a source of iNKT progenitors and a unique site of tissue dependent effector cell differentiation.https://elifesciences.org/articles/34793thymusiNKT cellsT cell development
spellingShingle Haiguang Wang
Kristin A Hogquist
CCR7 defines a precursor for murine iNKT cells in thymus and periphery
eLife
thymus
iNKT cells
T cell development
title CCR7 defines a precursor for murine iNKT cells in thymus and periphery
title_full CCR7 defines a precursor for murine iNKT cells in thymus and periphery
title_fullStr CCR7 defines a precursor for murine iNKT cells in thymus and periphery
title_full_unstemmed CCR7 defines a precursor for murine iNKT cells in thymus and periphery
title_short CCR7 defines a precursor for murine iNKT cells in thymus and periphery
title_sort ccr7 defines a precursor for murine inkt cells in thymus and periphery
topic thymus
iNKT cells
T cell development
url https://elifesciences.org/articles/34793
work_keys_str_mv AT haiguangwang ccr7definesaprecursorformurineinktcellsinthymusandperiphery
AT kristinahogquist ccr7definesaprecursorformurineinktcellsinthymusandperiphery