The thymic microenvironment differentially regulates development and trafficking of invariant NKT cell sublineages.

Autor:	Drennan MB; Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Ghent B-9000, Belgium; Michael.Drennan@ugent.be Dirk.Elewaut@ugent.be., Govindarajan S; Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Ghent B-9000, Belgium;, De Wilde K; Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Ghent B-9000, Belgium;, Schlenner SM; Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium;, Ware C; Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;, Nedospasov S; Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; and., Rodewald HR; Department for Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany., Elewaut D; Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Ghent B-9000, Belgium; Michael.Drennan@ugent.be Dirk.Elewaut@ugent.be.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Dec 15; Vol. 193 (12), pp. 5960-72. Date of Electronic Publication: 2014 Nov 07.
DOI:	10.4049/jimmunol.1401601
Abstrakt:	The regulatory role of the thymic microenvironment during trafficking and differentiation of the invariant NKT (iNKT) cell lineage remains poorly understood. In this study, we show that fractalkine receptor expression marks emigrating subpopulations of the NKT1, NKT2, and NKT17 sublineages in the thymus and peripheral organs of naive mice. Moreover, NKT1 sublineage cells can be subdivided into two subsets, namely NKT1(a) and NKT1(b), which exhibit distinct developmental and tissue-specific distribution profiles. More specifically, development and trafficking of the NKT1(a) subset are selectively dependent upon lymphotoxin (LT)α1β2-LTβ receptor-dependent differentiation of thymic stroma, whereas the NKT1(b), NKT2, and NKT17 sublineages are not. Furthermore, we identify a potential cellular source for LTα1β2 during thymic organogenesis, marked by expression of IL-7Rα, which promotes differentiation of the NKT1(a) subset in a noncell-autonomous manner. Collectively, we propose a mechanism by which thymic differentiation and retention of the NKT1 sublineage are developmentally coupled to LTα1β2-LTβ receptor-dependent thymic organogenesis. (Copyright © 2014 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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