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

Haiguang Wang, Kristin A. Hogquist

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere34793
JournaleLife
Volume7
DOIs
StatePublished - Aug 13 2018

Bibliographical note

Funding Information:
We thank Dr. Jason Schenkel (current affiliation: Brigham and Women’s Hospital) and Ms. Jane Ding for technical assistance, Drs. Stephen Jameson and You Jeong Lee (current affiliation: Pohang University of Science and Technology (POSTECH), Korea) for discussions and technical comments, and Dr. Henrique Borges da Silva and Mr. Dmitri Kotov for reviewing the manuscript. This research was supported by NIH grant R37 AI39560.

Funding Information:
We thank Dr. Jason Schenkel (current affiliation: Brigham and Women’s Hospital) and Ms. Jane Ding for technical assistance, Drs. Stephen Jameson and You Jeong Lee (current affiliation: Pohang Uni- versity of Science and Technology (POSTECH), Korea) for discussions and technical comments, and Dr. Henrique Borges da Silva and Mr. Dmitri Kotov for reviewing the manuscript. This research was supported by NIH grant R37 AI39560.

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