1. IL-18 is required for the T H 1-adaptation of T REG cells and the selective suppression of T H 17 responses in acute and chronic infections.
- Author
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Alvarez F, Istomine R, Da Silva Lira Filho A, Al-Aubodah TA, Huang D, Okde R, Olivier M, Fritz JH, and Piccirillo CA
- Subjects
- Humans, T-Lymphocytes, Regulatory, Interferon-gamma, Interleukin-12, Th17 Cells, Th1 Cells, Interleukin-18, Persistent Infection
- Abstract
Interleukin (IL)-18, a member of the IL-1 family of alarmins, is abundantly released in the lungs following influenza A (IAV) infections yet its role in orchestrating the local adaptive immune response remains ill defined. Through genetic disruption of the IL-18 receptor, we demonstrate that IL-18 not only promotes pulmonary T
H 1 responses but also influences regulatory T cells (TREG ) function in the infected lungs. As the response unfolds, TREG cells accumulating in the lungs express Helios, T-bet, CXCR3, and IL-18R1 and produce interferon γ in the presence of IL-12. During IAV, IL-18R1 is required for TREG cells to control TH 17, but not TH 1, responses and promote a return to lung homeostasis, revealing a novel mechanism of selective suppression. Moreover, this observation was not limited to the lungs, as skin-localized TREG cells require an IL-18 signal to specifically suppress IL-17A production by TH 17 and γδ T cells in a model of chronic cutaneous Leishmania major infection. Overall, these results uncover how IL-18 orchestrates the tissue adaptation of TREG cells to selectively favor TH 1 over TH 17 responses during TH 1-driven immune responses and provide a novel perspective into how IL-18 dictates the immune response during viral and parasitic infections., (Copyright © 2023. Published by Elsevier Inc.)- Published
- 2023
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