| First Author | Krishnamoorthy N | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 2 | Pages | e2206480120 |
| PubMed ID | 36595677 | Mgi Jnum | J:352194 |
| Mgi Id | MGI:7509055 | Doi | 10.1073/pnas.2206480120 |
| Citation | Krishnamoorthy N, et al. (2023) The Maresin 1-LGR6 axis decreases respiratory syncytial virus-induced lung inflammation. Proc Natl Acad Sci U S A 120(2):e2206480120 |
| abstractText | The resolution of infection is an active process with specific molecular and cellular mechanisms that temper inflammation and enhance pathogen clearance. Here, the specialized pro-resolving mediator (SPM) Maresin 1 (MaR1) inhibited respiratory syncytial virus (RSV)-induced inflammation. inlerleukin-13 production from type 2 innate lymphoid cells (ILC) and CD4 T helper type 2 cells was decreased by exogenous MaR1. In addition, MaR1 increased amphiregulin production and decreased RSV viral transcripts to promote resolution. MaR1 also promoted interferon-beta production in mouse lung tissues and also in pediatric lung slices. MaR1 significantly inhibited the RSV-triggered aberrant inflammatory phenotype in FoxP3-expressing Tregs. The receptor for MaR1, leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), was constitutively expressed on Tregs. Following RSV infection, mice lacking Lgr6 had exacerbated type 2 immune responses with an increased viral burden and blunted responses to MaR1. Together, these findings have uncovered a multi-pronged protective signaling axis for MaR1-Lgr6, improving Tregs's suppressive function and upregulating host antiviral genes resulting in decreased viral burden and pathogen-mediated inflammation, ultimately promoting restoration of airway mucosal homeostasis. |
