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Published in International immunology - 30 Sep 2019

Klibi J, Li S, Amable L, Joseph C, Brunet S, Delord M, Parietti V, Jaubert J, Marie J, Karray S, Eberl G, Lucas B, Toubert A, Benlagha K,

Link to Pubmed [PMID] – 31565740

Link to DOI – 10.1093/intimm/dxz064

Int Immunol 2020 02; 32(2): 105-116

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.

https://pubmed.ncbi.nlm.nih.gov/31565740