| First Author | Alvarez F | Year | 2023 |
| Journal | Mucosal Immunol | Volume | 16 |
| Issue | 4 | Pages | 462-475 |
| PubMed ID | 37182738 | Mgi Jnum | J:353160 |
| Mgi Id | MGI:7663215 | Doi | 10.1016/j.mucimm.2023.05.004 |
| Citation | Alvarez F, et al. (2023) 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. Mucosal Immunol 16(4):462-475 |
| abstractText | 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 (T(REG)) function in the infected lungs. As the response unfolds, T(REG) cells accumulating in the lungs express Helios, T-bet, CXCR3, and IL-18R1 and produce interferon gamma in the presence of IL-12. During IAV, IL-18R1 is required for T(REG) cells to control T(H)17, but not T(H)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 T(REG) cells require an IL-18 signal to specifically suppress IL-17A production by T(H)17 and gammadelta T cells in a model of chronic cutaneous Leishmania major infection. Overall, these results uncover how IL-18 orchestrates the tissue adaptation of T(REG) cells to selectively favor T(H)1 over T(H)17 responses during T(H)1-driven immune responses and provide a novel perspective into how IL-18 dictates the immune response during viral and parasitic infections. |
