IL-38 Ablation Reduces Local Inflammation and Disease Severity in Experimental Autoimmune Encephalomyelitis
- 1 March 2021
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 206 (5), 1058-1066
- https://doi.org/10.4049/jimmunol.2000923
Abstract
IL-38 is an IL-1 family receptor antagonist that restricts IL-17–driven inflammation by limiting cytokine production from macrophages and T cells. In the current study, we aimed to explore its role in experimental autoimmune encephalomyelitis in mice, which is, among others, driven by IL-17. Unexpectedly, IL-38–deficient mice showed strongly reduced clinical scores and histological markers of experimental autoimmune encephalomyelitis. This was accompanied by reduced inflammatory cell infiltrates, including macrophages and T cells, as well as reduced expression of inflammatory markers in the spinal cord. IL-38 was highly expressed by infiltrating macrophages in the spinal cord, and in vitro activated IL-38–deficient bone marrow–derived macrophages showed reduced expression of inflammatory markers, accompanied by altered cellular metabolism. These data suggest an alternative cell-intrinsic role of IL-38 to promote inflammation in the CNS.Keywords
This publication has 38 references indexed in Scilit:
- B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cellsThe Journal of Experimental Medicine, 2012
- Multiple sclerosisJCI Insight, 2012
- IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonistProceedings of the National Academy of Sciences, 2012
- CD161highCD8+T cells bear pathogenetic potential in multiple sclerosisBrain, 2011
- CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous systemBrain, 2009
- Glia-dependent TGF-β signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitisJCI Insight, 2007
- IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factorin vivoProceedings of the National Academy of Sciences, 2007
- CNS immune privilege: hiding in plain sightImmunological Reviews, 2006
- Identifying disease alleles by genome sharingNature Genetics, 1999
- A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H‐2b mice: Fine specificity and T cell receptor Vβ expression of encephalitogenic T cellsEuropean Journal of Immunology, 1995