title: Regulation of mouse NK cell development and function by cytokines.
abstract: Natural Killer (NK) cells are innate lymphocytes with an important role in the early defense against intracellular pathogens and against tumors. Like other immune cells, almost every aspects of their biology are regulated by cytokines. Interleukin (IL)-15 is pivotal for their development, homeostasis, and activation. Moreover, numerous other activating or inhibitory cytokines such as IL-2, IL-4, IL-7, IL-10, IL-12, IL-18, IL-21, Transforming growth factor-β (TGFβ) and type I interferons regulate their activation and their effector functions at different stages of the immune response. In this review we summarize the current understanding on the effect of these different cytokines on NK cell development, homeostasis, and functions during steady-state or upon infection by different pathogens. We try to delineate the cellular sources of these cytokines, the intracellular pathways they trigger and the transcription factors they regulate. We describe the known synergies or antagonisms between different cytokines and highlight outstanding questions in this field of investigation. Finally, we discuss how a better knowledge of cytokine action on NK cells could help improve strategies to manipulate NK cells in different clinical situations.
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon , Lyon , France ; U1111, INSERM , Lyon , France ; Ecole Normale Supérieure de Lyon , Lyon , France ; Centre International de Recherche en Infectiologie, Université Lyon 1 , Lyon , France ; UMR5308, CNRS , Lyon , France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Marçais
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon , Lyon , France ; U1111, INSERM , Lyon , France ; Ecole Normale Supérieure de Lyon , Lyon , France ; Centre International de Recherche en Infectiologie, Université Lyon 1 , Lyon , France ; UMR5308, CNRS , Lyon , France ; Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud , Lyon , France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Viel
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon , Lyon , France ; U1111, INSERM , Lyon , France ; Ecole Normale Supérieure de Lyon , Lyon , France ; Centre International de Recherche en Infectiologie, Université Lyon 1 , Lyon , France ; UMR5308, CNRS , Lyon , France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Grau
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon , Lyon , France ; U1111, INSERM , Lyon , France ; Ecole Normale Supérieure de Lyon , Lyon , France ; Centre International de Recherche en Infectiologie, Université Lyon 1 , Lyon , France ; UMR5308, CNRS , Lyon , France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henry
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon , Lyon , France ; U1111, INSERM , Lyon , France ; Ecole Normale Supérieure de Lyon , Lyon , France ; Centre International de Recherche en Infectiologie, Université Lyon 1 , Lyon , France ; UMR5308, CNRS , Lyon , France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon , Lyon , France ; U1111, INSERM , Lyon , France ; Ecole Normale Supérieure de Lyon , Lyon , France ; Centre International de Recherche en Infectiologie, Université Lyon 1 , Lyon , France ; UMR5308, CNRS , Lyon , France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
keywords: TGF-beta; cytotoxicity; interferons; interleukin-12; interleukin-15; interleukin-18; natural killer cells; signal transduction