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

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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.

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All relevant data are included in the manuscripts and supporting files. Source data files have been provided.

Article and author information

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Haiguang Wang

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5403-9179
Kristin A Hogquist

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States

For correspondence
hogqu001@umn.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9963-5687

Funding

NIH NIAID (R37 AI39560)

Kristin A Hogquist

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. This protocol was approved by the Institutional Animal Care and Use Committee of the University of Minnesota (protocol #s1706-34889A and 1502-32279A).

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.