Extrinsic allospecific signals of hematopoietic origin dictate iNKT cell lineage-fate decisions during development.
Extrinsic allospecific signals of hematopoietic origin dictate iNKT cell lineage-fate decisions during development.
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DOI：
10.1038/srep28837
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发表时间：
2016-06-29
影响因子：
4.6
通讯作者：
Shaaban AF
中科院分区：
文献类型：
--
作者：
Strong BSI;Newkold TJ;Lee AE;Turner LE;Alhajjat AM;Heusel JW;Shaaban AF
不变的 NKT (iNKT) 细胞对于维持对出生后遇到的同种异体抗原的耐受性至关重要，这表明存在自我教育过程。然而，尚未描述发育过程中遇到的同种异体抗原对塑造 iNKT 细胞表型和功能的影响。为了更好地理解这一过程，当前的报告检查了幼稚 iNKT 细胞在同种异体环境中成熟的过程。在年龄匹配的同种异体小鼠胎儿之间进行胎儿造血细胞的产前转移后，细胞外在信号似乎决定了 Ly49 受体表达的同种异体特异性模式和发育中的 iNKT 细胞的谱系多样性。这一过程的调节来自造血来源的细胞，只需很少的暴露即可促进 iNKT 细胞发育中的广泛变化。这些发现强调了 iNKT 细胞在同种异体环境中发育和成熟时令人惊讶的不对称同种异体改变，并为 iNKT 细胞自我教育的研究建立了新的范例。
Invariant NKT (iNKT) cells are critical to the maintenance of tolerance toward alloantigens encountered during postnatal life pointing to the existence of a process for self-education. However, the impact of developmentally encountered alloantigens in shaping the phenotype and function of iNKT cells has not been described. To better understand this process, the current report examined naïve iNKT cells as they matured in an allogeneic environment. Following the prenatal transfer of fetal hematopoietic cells between age-matched allogeneic murine fetuses, cell-extrinsic signals appeared to dictate allospecific patterns of Ly49 receptor expression and lineage diversity in developing iNKT cells. Regulation for this process arose from cells of hematopoietic origin requiring only rare exposure to facilitate broad changes in developing iNKT cells. These findings highlight surprisingly asymmetric allospecific alterations in iNKT cells as they develop and mature in an allogeneic environment and establish a new paradigm for study of the self-education of iNKT cells.