Group 1 ILCs regulate T cell-mediated liver immunopathology by controlling local IL-2 availability

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 JD, Bousso P, Gilmore SA, Khan S, Baca M, Vivier E, Gasteiger G, Kuka M, Guidotti LG, Iannacone M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Science immunology American Association for the Advancement of Science

Book Volume: 7

Article Number: eabi6112

Journal Issue: 68

DOI: 10.1126/sciimmunol.abi6112

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.

Involved external institutions

Università Vita-Salute San Raffaele (UniSR) IT Italy (IT) Julius-Maximilians-Universität Würzburg DE Germany (DE) Sangamo Therapeutics, Inc US United States (USA) (US) Institut Pasteur FR France (FR) Gilead Sciences, Inc. US United States (USA) (US) Aix-Marseille University / Aix-Marseille Université FR France (FR)

How to cite

APA:

Fumagalli, V., Venzin, V., Di Lucia, P., Moalli, F., Ficht, X., Ambrosi, G.,... Iannacone, M. (2022). Group 1 ILCs regulate T cell-mediated liver immunopathology by controlling local IL-2 availability. Science immunology, 7(68). https://doi.org/10.1126/sciimmunol.abi6112

MLA:

Fumagalli, Valeria, et al. "Group 1 ILCs regulate T cell-mediated liver immunopathology by controlling local IL-2 availability." Science immunology 7.68 (2022).

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