Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets.
Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets.
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DOI：
10.4049/jimmunol.1700214
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发表时间：
2017-07-01
期刊：
影响因子：
--
通讯作者：
Dougan SK
中科院分区：
文献类型：
--
作者：
Clancy-Thompson E;Chen GZ;Tyler PM;Servos MM;Barisa M;Brennan PJ;Ploegh HL;Dougan SK
iNKT细胞功能亚群由关键转录因子和细胞因子如IL-4、ifn - γ、IL-17和IL-10的输出来定义。为了研究TCR特异性如何决定iNKT功能，我们使用体细胞核移植产生了三种从iNKT细胞核克隆的小鼠。每个系使用不变的Vα14Jα18 TCRα，与唯一的Vβ7或Vβ8.2亚基配对。我们检测了组织归巢、PLZF、T-bet和RORγt的表达以及细胞因子谱，发现尽管单克隆iNKT细胞分化为所有功能亚群，但NKT17谱系根据TCR的表达而减少或扩增。我们在有限稀释的骨髓嵌合体中检测了iNKT胸腺发育，结果表明，较高的TCR亲切度与较高的PLZF和降低的T-bet表达相关。iNKT功能亚群表现出不同的组织分布模式。尽管每个单克隆TCR个体在所有组织中都表现出固有的亚群分布偏好，但iNKT细胞因子谱在组织来源方面的差异大于TCR特异性。
iNKT cell functional subsets are defined by key transcription factors and output of cytokines such as IL-4, IFNγ, IL-17, and IL-10. To examine how TCR specificity determines iNKT function, we used somatic cell nuclear transfer to generate three lines of mice, cloned from iNKT nuclei. Each line uses the invariant Vα14Jα18 TCRα, paired with unique Vβ7 or Vβ8.2 subunits. We examined tissue homing, expression of PLZF, T-bet, and RORγt, as well as cytokine profiles and found that although monoclonal iNKT cells differentiated into all functional subsets, the NKT17 lineage was reduced or expanded depending on the TCR expressed. We examined iNKT thymic development in limited dilution bone marrow chimeras and show that higher TCR avidity correlates with higher PLZF and reduced T-bet expression. iNKT functional subsets showed distinct tissue distribution patterns. Although each individual monoclonal TCR showed an inherent subset distribution preference that was evident across all tissues examined, the iNKT cytokine profile differed more by tissue of origin than by TCR specificity.
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