| First Author | Kanai K | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 8 | Pages | 2703-2713 |
| PubMed ID | 29500240 | Mgi Jnum | J:261546 |
| Mgi Id | MGI:6151592 | Doi | 10.4049/jimmunol.1700412 |
| Citation | Kanai K, et al. (2018) Murine gamma-Herpesvirus 68 Induces Severe Lung Inflammation in IL-27-Deficient Mice with Liver Dysfunction Preventable by Oral Neomycin. J Immunol 200(8):2703-2713 |
| abstractText | IL-27 is an immunoregulatory cytokine consisting of p28 and EBI3. Its receptor also has two subunits, WSX1 and gp130. Although IL-27 promotes Th1 differentiation in naive T cells, it also induces IL-10 expression in effector Th1 cells to curtail excessive immune responses. By using p28-deficient mice and WSX1-deficient mice (collectively called IL-27-deficient mice), we examined the role of IL-27 in primary infection by murine gamma-herpesvirus 68 (MHV68), a murine model of EBV. Upon airway infection with MHV68, IL-27-deficient mice had more aggravated lung inflammation than wild-type mice, although MHV68 infection per se was better controlled in IL-27-deficient mice. Although epithelial cells and alveolar macrophages were primarily infected by MHV68, interstitial macrophages and dendritic cells were the major producers of IL-27. The lung inflammation of IL-27-deficient mice was characterized by more IFN-gamma-producing CD8(+) T cells and fewer IL-10-producing CD8(+) T cells than that of wild-type mice. An infectious mononucleosis-like disease was also aggravated in IL-27-deficient mice, with prominent splenomegaly and severe hepatitis. Infiltration of IFN-gamma-producing effector cells and upregulation of the CXCR3 ligand chemokines CXCL9, CXCL10, and CXCL11 were noted in the liver of MHV68-infected mice. Oral neomycin effectively ameliorated hepatitis, with decreased production of these chemokines in the liver, suggesting that the intestinal microbiota plays a role in liver inflammation through upregulation of these chemokines. Collectively, IL-27 is essential for the generation of IL-10-producing effector cells in primary infection by MHV68. Our findings may also provide new insight into the mechanism of hepatitis associated with infectious mononucleosis. |
