期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 50, 页码 19845-19850出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0806472105
关键词
thymic precursors; alpha-GalCer; CD1d; cytokines
资金
- Centre National de la Recherche Scientifique
- Universite Rene Descartes - Paris V
- Agence Nationale de Recherches Microbiologie-Maladie Emergentes [ASTHMA-IL-17]
- Fondation pour la Recherche Medicale
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
Invariant natural killer T (iNKT) cells constitute a subpopulation of T cells that recognize glycolipids presented by CD1d molecules. They are characterized by their prompt production of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), which enables them to modulate diverse immune responses. Recently, we enlarged this concept by identifying a distinct IL-17-producing iNKT cell subset, named iNKT17 cells. The mechanisms leading to the acquisition of this new iNKT cell activity are unknown. Herein we show that IL-17-producing iNKT cells are already present in the thymus, predominantly among a subset regarded so far as an immature stage of thymic iNKT cell development, the CD1d tetramer(pos)CD44(pos)NK1.1(neg)CD4(neg) cells. Using EGFP reporter mice, we demonstrate that the transcription factor ROR-gamma t is critical for the thymic differentiation of this subset because only ROR-gamma t(pos) iNKT cells are capable of massively secreting IL-17. Moreover, IL-17-producing CD1d tetramer(pos)CD44(pos)NK1.1(neg)CD4(neg) thymic iNKT cells have reached a mature differentiation stage because they fail to generate other cell subsets in fetal thymic organ culture. Conversely, thymic ROR-gamma t(neg) iNKT cell precursors give rise to progeny, but acquire neither ROR-gamma t expression nor the ability to secrete IL-17. In conclusion, our findings demonstrate an alternative thymic pathway leading to the development of iNKT17 cells that requires ROR-gamma t expression.
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