INSERM, UMR-1160, Institut Universitaire d'Hématologie, Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Int Immunol. 2020 Feb 7;32(2):105-116. doi: 10.1093/intimm/dxz064.
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.
表达维甲酸受体相关孤儿受体γt（RORγt）并产生白细胞介素-17的不变自然杀伤 T（iNKT）细胞代表 C57BL/6J（B6）小鼠中 CD1d 限制性 iNKT 细胞（iNKT17）的一个亚群。在本研究中，我们旨在确定它们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高的凋亡倾向。这些细胞不太可能存在于胸腺中，表明胸腺迁出和更高的凋亡潜力可能导致 RORγt+iNKT 细胞减少胸腺分布。个体发生研究表明，成熟的 HSAlow RORγt+iNKT 细胞可能通过在表达 CCR6 和 CD138 时表现出差异表达的不同发育阶段发育而来，在此期间，RORγt 表达和白细胞介素-17 产生能力逐渐获得。最后，我们发现 RORγt+iNKT 细胞感知到强烈的 TCR 信号，这可能有助于它们进入特定的“Th17 样”发育程序，影响它们的存活和迁移。总的来说，我们的研究提出了 iNKT17 细胞的假设性胸腺发育序列，这对于研究调节该发育程序的分子机制非常有用。
