ILCs are early effectors of immunity and provide a means to rapidly respond to infection or inflammation, and are distinguished from T and B cells of the adaptive immune response. Three groups of ILCs are now described: ILC1, ILC2 and ILC3. ILC1 consists of NK cells and other interferon-g producing innate lymphocytes characterized by expression of the transcription factors T-bet and/Eomes. ILC2 secrete ‘TH2-like’ cytokines under the control of the transcription factors GATA-3 and RORa. ILC3 includes several phenotypically distinct cells that express and require the transcription factor RORgt in order to produce notably the cytokines IL-17 and IL-22. These ILC subsets have been implicated in a wide range of physiological processes including tissue homeostasis and repair, immune defense or development of lymphoid organs.
In this project, we aim to understand the signals that regulate human ILC development from hematopoietic precursors. We utilise both in vitro culture techniques (bulk and single cell cloning) as well as innovative in vivo approaches (humanized mice) to study this process. Our recent results identify a systemically distributed human ILC precursor that can give rise to all ILC subsets, including cytotoxic NK cells. Furthermore, environmental signals condition ILC differentiation, resulting in substantial functional plasticity. These observations suggest that manipulation of ILC subsets in human disease settings may be of therapeutic benefit.
Lim, A.I., Verrier, T., Vosshenrich, C.A.J. and Di Santo, J.P. (2017) Developmental options and functional plasticity of innate lymphoid cells. Current Opinion in Immunology
Lim, A.-I., Menegatti, S., Bustamante, J., Le Bourhis, L., Allez, M., Rogge, L., Casanova, J.-L., Yssel, H. and Di Santo, J.P. (2016) IL-12 drives functional plasticity of human group 2 innate lymphoid cells. Journal of Experimental Medicine 213:569-583.