| First Author | Lundström W | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 19 | Pages | E1761-70 |
| PubMed ID | 23610432 | Mgi Jnum | J:197346 |
| Mgi Id | MGI:5492202 | Doi | 10.1073/pnas.1222303110 |
| Citation | Lundstrom W, et al. (2013) Soluble IL7Ralpha potentiates IL-7 bioactivity and promotes autoimmunity. Proc Natl Acad Sci U S A 110(19):E1761-70 |
| abstractText | Human soluble interleukin-7 receptor (sIL7R)alpha circulates in high molar excess compared with IL-7, but its biology remains unclear. We demonstrate that sIL7Ralpha has moderate affinity for IL-7 but does not bind thymic stromal lymphopoietin. Functionally, sIL7Ralpha competes with cell-associated IL-7 receptor to diminish excessive IL-7 consumption and, thus, enhances the bioactivity of IL-7 when the cytokine is limited, as it is presumed to be in vivo. IL-7 signaling in the presence of sIL7Ralpha also diminishes expression of CD95 and suppressor of cytokine signaling 1, both regulatory molecules. Murine models confirm diminished consumption of IL-7 in the presence of sIL7Ralpha and also demonstrate a potentiating effect of sIL7Ralpha on IL-7-mediated homeostatic expansion and experimental autoimmune encephalomyelitis exacerbation. In multiple sclerosis and several other autoimmune diseases, IL7R genotype influences susceptibility. We measured increased sIL7Ralpha levels, as well as increased IL-7 levels, in multiple sclerosis patients with the predisposing IL7R genotype, consistent with diminished IL-7 consumption in vivo. This work demonstrates that sIL7Ralpha potentiates IL-7 bioactivity and provides a basis to explain the increased risk of autoimmunity observed in individuals with genotype-induced elevations of sIL7Ralpha. |
