Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells

Ana Raykova, Paolo Carrega, Frank M. Lehmann, Robert Ivanek, Vanessa Landtwing, Isaak Josef Quast, Jan D. Lünemann, Daniela Finke, Guido Ferlazzo, Obinna Chijioke, Christian Münz

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34 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2679-2691
Number of pages13
JournalBlood Advances
Issue number27
Publication statusPublished - 26 Dec 2017

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