| First Author | Zhang M | Year | 2021 |
| Journal | J Immunol | PubMed ID | 34789557 |
| Mgi Jnum | J:317180 | Mgi Id | MGI:6849892 |
| Doi | 10.4049/jimmunol.2100655 | Citation | Zhang M, et al. (2021) IL-13 Controls IL-33 Activity through Modulation of ST2. J Immunol 207(12):3070-3080 |
| abstractText | IL-33 is a multifunctional cytokine that mediates local inflammation upon tissue damage. IL-33 is known to act on multiple cell types including group 2 innate lymphoid cells (ILC2s), Th2 cells, and mast cells to drive production of Th2 cytokines including IL-5 and IL-13. IL-33 signaling activity through transmembrane ST2L can be inhibited by soluble ST2 (sST2), which acts as a decoy receptor. Previous findings suggested that modulation of IL-13 levels in mice lacking decoy IL-13Ralpha2, or mice lacking IL-13, impacted responsiveness to IL-33. In this study, we used Il13 (-/-) mice to investigate whether IL-13 regulates IL-33 activity by modulating the transmembrane and soluble forms of ST2. In Il13 (-/-) mice, the effects of IL-33 administration were exacerbated relative to wild type (WT). Il13 (-/-) mice administered IL-33 i.p. had heightened splenomegaly, more immune cells in the peritoneum including an expanded ST2L(+) ILC2 population, increased eosinophilia in the spleen and peritoneum, and reduced sST2 in the circulation and peritoneum. In the spleen, lung, and liver of mice given IL-33, gene expression of both isoforms of ST2 was increased in Il13 (-/-) mice relative to WT. We confirmed fibroblasts to be an IL-13-responsive cell type that can regulate IL-33 activity through production of sST2. This study elucidates the important regulatory activity that IL-13 exerts on IL-33 through induction of IL-33 decoy receptor sST2 and through modulation of ST2L(+) ILC2s. |
