| First Author | Barik S | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 7 | Pages | 2236-2248 |
| PubMed ID | 28801358 | Mgi Jnum | J:251613 |
| Mgi Id | MGI:6103622 | Doi | 10.4049/jimmunol.1700372 |
| Citation | Barik S, et al. (2017) IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis. J Immunol 199(7):2236-2248 |
| abstractText | IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Ralpha/IL-13Ralpha1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R(-/-)) are more susceptible to experimental allergic encephalomyelitis than mice sufficient for the HR (13R(+/+)) and develop early onset and more severe disease. Moreover, Th17 cells from 13R(-/-) mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R(+/+) mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression, leading to control of immune-mediated CNS inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity. |
