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Characterization of the developmental landscape of murine RORγt+ iNKT cells.
International Immunology ( IF 4.8 ) Pub Date : 2020-02-07 , DOI: 10.1093/intimm/dxz064
Jihene Klibi 1, 2 , Shamin Li 1, 2 , Ludivine Amable 1, 2 , Claudine Joseph 1, 2 , Stéphane Brunet 1, 2 , Marc Delord 3 , Veronique Parietti 2, 4 , Jean Jaubert 5 , Julien Marie 6 , Saoussen Karray 1, 2 , Gerard Eberl 7, 8 , Bruno Lucas 9 , Antoine Toubert 1, 2 , Kamel Benlagha 1, 2
Affiliation  

Invariant natural killer T (iNKT) cells expressing the retinoic acid receptor-related orphan receptor γt (RORγt) and producing IL-17 represent a minor subset of CD1d-restricted iNKT cells (iNKT17) in C57BL/6J (B6) mice. We aimed in this study to define the reasons for their low distribution and the sequence of events accompanying their normal thymic development. We found that RORγt+ iNKT cells have higher proliferation potential and a greater propensity to apoptosis than RORγt- iNKT cells. These cells do not likely reside in the thymus indicating that thymus emigration, and higher apoptosis potential, could contribute to RORγt+ iNKT cell reduced thymic distribution. Ontogeny studies suggest that mature HSAlow RORγt+ iNKT cells might develop through developmental stages defined by a differential expression of CCR6 and CD138 during which RORγt expression and IL-17 production capabilities are progressively acquired. Finally, we found that RORγt+ iNKT cells perceive a strong TCR signal that could contribute to their entry into a specific 'Th17 like' developmental program influencing their survival and migration. Overall, our study proposes a hypothetical thymic developmental sequence for iNKT17 cells, which could be of great use to study molecular mechanisms regulating this developmental program.

中文翻译:

鼠RORγt+ iNKT细胞的发育情况的表征。

在C57BL / 6J(B6)小鼠中,表达视黄酸受体相关孤儿受体γt(RORγt)并产生IL-17的不变自然杀伤T细胞(iNKT)代表CD1d限制性iNKT细胞(iNKT17)的一小部分。在这项研究中,我们旨在确定其分布低的原因以及伴随其正常胸腺发育的事件顺序。我们发现,RORγt+ iNKT细胞比RORγt-iNKT细胞具有更高的增殖潜力和更大的凋亡倾向。这些细胞不太可能驻留在胸腺中,这表明胸腺迁移和更高的凋亡潜力可能有助于RORγt+ iNKT细胞减少胸腺分布。个体发育研究表明,成熟的HSAlowRORγt+ iNKT细胞可能会通过CCR6和CD138差异表达所定义的发育阶段发展,在此期间逐渐获得RORγt表达和IL-17的生产能力。最终,我们发现RORγt+ iNKT细胞感知到强TCR信号,这可能有助于它们进入影响其生存和迁移的特定“ Th17样”发育程序。总体而言,我们的研究提出了iNKT17细胞假想的胸腺发育序列,这可能对研究调节该发育程序的分子机制有很大的帮助。影响其生存和迁移的发展计划。总体而言,我们的研究提出了iNKT17细胞假想的胸腺发育序列,这可能对研究调节该发育程序的分子机制有很大的帮助。影响其生存和迁移的发展计划。总体而言,我们的研究提出了iNKT17细胞假想的胸腺发育序列,这可能对研究调节该发育程序的分子机制有很大的帮助。
更新日期:2019-11-01
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