TY - JOUR
T1 - Lineage relationships of human interleukin-22-producing CD56+ RORgt1 innate lymphoid cells and conventional natural killer cells
AU - Ahn, Yong Oon
AU - Blazar, Bruce R.
AU - Miller, Jeffrey S.
AU - Verneris, Michael R.
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
N2 - Human interleukin (IL)-22-producing RORgt+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 (CD561/2 CD117highCD942). Using an in vitro differentiation and primary human tissues, we investigated their developmental relationships. cNK cells showed a CD561CD1171CD71/2 LFA-1high phenotype and expressed surface receptors, cytokines, and transcription factors found on mature cNK cells. In contrast, ILC22 cells were contained within the CD561CD117highCD942CD72LFA-12 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-g production or cytotoxic responses. Most purified CD561CD1171CD71/2LFA-12 remained as ILC22 cells and never became cNK cells. In the absence of IL-15, CD341 cells showed a complete block in cNK differentiation and instead gave rise to a CD561 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.
AB - Human interleukin (IL)-22-producing RORgt+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 (CD561/2 CD117highCD942). Using an in vitro differentiation and primary human tissues, we investigated their developmental relationships. cNK cells showed a CD561CD1171CD71/2 LFA-1high phenotype and expressed surface receptors, cytokines, and transcription factors found on mature cNK cells. In contrast, ILC22 cells were contained within the CD561CD117highCD942CD72LFA-12 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-g production or cytotoxic responses. Most purified CD561CD1171CD71/2LFA-12 remained as ILC22 cells and never became cNK cells. In the absence of IL-15, CD341 cells showed a complete block in cNK differentiation and instead gave rise to a CD561 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.
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U2 - 10.1182/blood-2012-07-440099
DO - 10.1182/blood-2012-07-440099
M3 - Article
C2 - 23327921
AN - SCOPUS:84877930373
SN - 0006-4971
VL - 121
SP - 2234
EP - 2243
JO - Blood
JF - Blood
IS - 12
ER -