TY - JOUR
T1 - Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells
AU - Raykova, Ana
AU - Carrega, Paolo
AU - Lehmann, Frank M.
AU - Ivanek, Robert
AU - Landtwing, Vanessa
AU - Quast, Isaak
AU - Lunemann, Jan D.
AU - Finke, Daniela
AU - Ferlazzo, Guido
AU - Chijioke, Obinna
AU - Munz, Christian
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/12/26
Y1 - 2017/12/26
N2 - Type 3 innate lymphoid cells (ILC3s) fulfill protective functions at mucosal surfaces via cytokine production. Although their plasticity to become ILC1s, the innate counterparts of type 1 helper T cells, has been described previously, we report that they can differentiate into cytotoxic lymphocytes with many characteristics of early differentiated natural killer (NK) cells. This transition is promoted by the proinflammatory cytokines interleukin 12 (IL-12) and IL-15, and correlates with expression of the master transcription factor of cytotoxicity, eomesodermin (Eomes). As revealed by transcriptome analysis and flowcytometric profiling, differentiated ILC3s express CD94, NKG2A, NKG2C, CD56, and CD16 among other NK-cell receptors, and possess all components of the cytotoxic machinery. These characteristics allow them to recognize and kill leukemic cells with perforin and granzymes. Therefore, ILC3s can be harnessed for cytotoxic responses via differentiation under the influence of proinflammatory cytokines.
AB - Type 3 innate lymphoid cells (ILC3s) fulfill protective functions at mucosal surfaces via cytokine production. Although their plasticity to become ILC1s, the innate counterparts of type 1 helper T cells, has been described previously, we report that they can differentiate into cytotoxic lymphocytes with many characteristics of early differentiated natural killer (NK) cells. This transition is promoted by the proinflammatory cytokines interleukin 12 (IL-12) and IL-15, and correlates with expression of the master transcription factor of cytotoxicity, eomesodermin (Eomes). As revealed by transcriptome analysis and flowcytometric profiling, differentiated ILC3s express CD94, NKG2A, NKG2C, CD56, and CD16 among other NK-cell receptors, and possess all components of the cytotoxic machinery. These characteristics allow them to recognize and kill leukemic cells with perforin and granzymes. Therefore, ILC3s can be harnessed for cytotoxic responses via differentiation under the influence of proinflammatory cytokines.
UR - http://www.scopus.com/inward/record.url?scp=85051092935&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2017008839
DO - 10.1182/bloodadvances.2017008839
M3 - Article
AN - SCOPUS:85051092935
SN - 2473-9529
VL - 1
SP - 2679
EP - 2691
JO - Blood advances
JF - Blood advances
IS - 27
ER -