title: IL-17-producing invariant NKT cells in lymphoid organs are recent thymic emigrants identified by neuropilin-1 expression.
abstract: Despite increasing knowledge on the mechanisms of invariant natural killer T (iNKT)-cell development in the thymus, the function of recent thymic emigrant (RTE) iNKT cells remains largely unexplored, principally because of a lack of bona fide markers to distinguish RTE from long-lived iNKT cells. Whether the recently described IL-17-producing iNKT cell subset is part of RTE has notably not been addressed. In the present study, we show that neuropilin-1 (Nrp-1), a transmembrane receptor mainly found on T-regulatory (Treg) cells in the murine immune system, is specifically expressed on RTE iNKT cells in naive mice. We used the Nrp-1 marker to discriminate RTE from mature iNKT cells and compare their functions. We show that RTE iNKT cells proliferate more than mature iNKT cells after in vitro activation; that, unlike mature iNKT cells, most RTE iNKT cells fail to rapidly produce IFN-γ and IL-4 after in vivo activation; and, most importantly, that IL-17-producing iNKT cells in lymphoid organs of naive mice are contained within the RTE iNKT cell pool. Our results establish an accurate marker of RTE iNKT cells and reveal that continuous thymic output is required for pro-inflammatory IL-17 secretion, a key function of adult iNKT cells.
authors.affiliation: Centre National de la Recherche Scientifique, Université Paris Descartes, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Milpied
authors.forename: Bérangère
authors.initials: B
authors.lastname: Massot
authors.forename: Amédée
authors.initials: A
authors.lastname: Renand
authors.forename: Séverine
authors.initials: S
authors.lastname: Diem
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
authors.forename: Maria
authors.initials: M
authors.lastname: Leite-de-Moraes
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Rubio
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000818:Animals; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D020381:Interleukin-17 / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D039942:Neuropilin-1 / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D020381:Interleukin-17; D039942:Neuropilin-1