1. Group 1 ILCs regulate T cell–mediated liver immunopathology by controlling local IL-2 availability
- Author
-
Valeria Fumagalli, Valentina Venzin, Pietro Di Lucia, Federica Moalli, Xenia Ficht, Gioia Ambrosi, Leonardo Giustini, Francesco Andreata, Marta Grillo, Diletta Magini, Micol Ravà, Christin Friedrich, Jason D. Fontenot, Philippe Bousso, Sarah A. Gilmore, Shahzada Khan, Manuel Baca, Eric Vivier, Georg Gasteiger, Mirela Kuka, Luca G. Guidotti, Matteo Iannacone, IRCCS San Raffaele Scientific Institute [Milan, Italie], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Max Planck Research Group - The Julius-Maximiliams-Universität Würzburg, Sangamo Therapeutics brisbane, Dynamiques des Réponses immunes - Dynamics of Immune Responses, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Gilead Sciences, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innate Pharma, Hôpital de la Timone [CHU - APHM] (TIMONE), ANR-17-RHUS-0007,PIONEER,Precision Immuno-Oncology for advanced Non small cell lung cancer patients with PD-1 ICI Resistance(2017), Fumagalli, V, Venzin, V, Di Lucia, P, Moalli, F, Ficht, X, Ambrosi, G, Giustini, L, Andreata, F, Grillo, M, Magini, D, Rava, M, Friedrich, C, Fontenot, J, Bousso, P, Gilmore, S, Khan, S, Baca, M, Vivier, E, Gasteiger, G, Kuka, M, Guidotti, L, Iannacone, M, Fumagalli, V., Venzin, V., Di Lucia, P., Moalli, F., Ficht, X., Ambrosi, G., Giustini, L., Andreata, F., Grillo, M., Magini, D., Rava, M., Friedrich, C., Fontenot, J. D., Bousso, P., Gilmore, S. A., Khan, S., Baca, M., Vivier, E., Gasteiger, G., Kuka, M., Guidotti, L. G., and Iannacone, M.
- Subjects
Mice, Inbred BALB C ,Interleukin-2 (IL-2) ,[SDV]Life Sciences [q-bio] ,Immunology ,Mice, Transgenic ,General Medicine ,CD8-Positive T-Lymphocytes ,Immunity, Innate ,Hepatitis B Virus (HBV) ,Killer Cells, Natural ,Mice, Inbred C57BL ,Mice ,Mice, Congenic ,Group 1 innate lymphoid cells (ILCs) ,Animals ,Interleukin-2 ,Lymphocytes - Abstract
Group 1 innate lymphoid cells (ILCs), which comprise both natural killer (NK) cells and ILC1s, are important innate effectors that can also positively and negatively influence adaptive immune responses. The latter function is generally ascribed to the ability of NK cells to recognize and kill activated T cells. Here, we used multiphoton intravital microscopy in mouse models of hepatitis B to study the intrahepatic behavior of group 1 ILCs and their cross-talk with hepatitis B virus (HBV)–specific CD8+T cells. We found that hepatocellular antigen recognition by effector CD8+T cells triggered a prominent increase in the number of hepatic NK cells and ILC1s. Group 1 ILCs colocalized and engaged in prolonged interactions with effector CD8+T cells undergoing hepatocellular antigen recognition; however, they did not induce T cell apoptosis. Rather, group 1 ILCs constrained CD8+T cell proliferation by controlling local interleukin-2 (IL-2) availability. Accordingly, group 1 ILC depletion, or genetic removal of their IL-2 receptor a chain, considerably increased the number of intrahepatic HBV-specific effector CD8+T cells and the attendant immunopathology. Together, these results reveal a role for group 1 ILCs in controlling T cell–mediated liver immunopathology by limiting local IL-2 concentration and have implications for the treatment of chronic HBV infection.
- Published
- 2022
- Full Text
- View/download PDF