10.3389/fimmu.2018.01252.s003
Thibaut Perchet
Thibaut
Perchet
Maxime Petit
Maxime
Petit
Elena-Gaia Banchi
Elena-Gaia
Banchi
Sylvain Meunier
Sylvain
Meunier
Ana Cumano
Ana
Cumano
Rachel Golub
Rachel
Golub
Image_3_The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions.tif
Frontiers
2018
Notch
innate lymphoid cells
liver
cancer
inflammation
transcription factors
cytotoxicity
molecular biology techniques
2018-06-07 04:03:04
Figure
https://frontiersin.figshare.com/articles/figure/Image_3_The_Notch_Signaling_Pathway_Is_Balancing_Type_1_Innate_Lymphoid_Cell_Immune_Functions_tif/6453431
<p>The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC). We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK) cells and type 1 helper innate lymphoid cells (ILC1) that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.</p>