Lineage relationships of human interleukin-22-producing CD56+ RORγt+ innate lymphoid cells and conventional natural killer cells
Lineage relationships of human interleukin-22-producing CD56+ RORγt+ innate lymphoid cells and conventional natural killer cells
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DOI：
10.1182/blood-2012-07-440099
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发表时间：
2013-03-21
期刊：
影响因子：
20.3
通讯作者：
Verneris, Michael R.
中科院分区：
文献类型：
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作者：
Ahn, Yong-Oon;Blazar, Bruce R.;Verneris, Michael R.
次级淋巴组织中存在产生人白细胞介素（IL）-22的ROR γ t（+）先天淋巴细胞（ILC 22）和常规自然杀伤（cNK）细胞。两者均具有对应于III期NK祖细胞的免疫表型（CD 56（+/-）CD 117（高）CD 94（-））。利用体外分化和原代人体组织，我们研究了它们的发育关系。cNK细胞显示出CD 56（+）CD 117（+）CD 7（+/-）LFA-1（高）表型，并表达成熟cNK细胞上发现的表面受体、细胞因子和转录因子。相反，ILC 22细胞包含在CD 56（+）CD 117（高）CD 94（-）CD 7（-）LFA-1（-）组分中，并产生IL-22、IL-8和粒细胞巨噬细胞集落刺激因子。虽然ILC 22细胞表达NKp 44和CD 161，但它们缺乏大多数其他NK受体和NK相关转录因子（T-bet和Eomes），并且不能产生干扰素γ或细胞毒性反应。大多数纯化的CD 56（+）CD 117（+）CD 7（+/-）LFA-1（-）仍为ILC 22细胞，从未成为cNK细胞。在不存在IL-15的情况下，CD 34（+）细胞显示cNK分化的完全阻断，而是产生ILC 22细胞的CD 56（+）群体。相反，在不存在IL-7和干细胞因子的情况下，产生了cNK细胞，但ILC 22细胞显示出最小的分化。尽管人ILC 22细胞和cNK祖细胞具有与III期NK祖细胞重叠的表型，但它们具有独特的细胞因子需求，并且可以通过LFA-1表达来区分。
Human interleukin (IL)-22-producing ROR gamma t(+) innate lymphoid cells (ILC22) and conventional natural killer (cNK) cells are present in secondary lymphoid tissues. Both have an immunophenotype corresponding to stage III NK progenitors (CD56(+/-) CD117(high)CD94(-)). Using an in vitro differentiation and primary human tissues, we investigated their developmental relationships. cNK cells showed a CD56(+)CD117(+)CD7(+/-) LFA-1(high) phenotype and expressed surface receptors, cytokines, and transcription factors found on mature cNK cells. In contrast, ILC22 cells were contained within the CD56(+)CD117(high)CD94(-)CD7(-)LFA-1(-) fraction and produced IL-22, IL-8, and granulocyte macrophage colony stimulating factor. Although ILC22 cells expressed NKp44 and CD161, they lacked most other NK receptors and NK-associated transcription factors (T-bet and Eomes) and were incapable of interferon-gamma production or cytotoxic responses. Most purified CD56(+)CD117(+)CD7(+/-) LFA-1(-) remained as ILC22 cells and never became cNK cells. In the absence of IL-15, CD34(+) cells showed a complete block in cNK differentiation and instead gave rise to a CD56(+) population of ILC22 cells. Conversely, in the absence of IL-7 and stem cell factor, cNK cells were generated but ILC22 cells showed minimal differentiation. Although human ILC22 cells and cNK progenitors have a phenotype that overlaps with stage III NK progenitors, they have unique cytokine requirements and can be distinguished by LFA-1 expression.