Abstract
Single-nucleotide polymorphisms close to IL22RA2, coding for the soluble interleukin (IL)-22-binding protein (IL-22BP), are strongly and reproducibly associated with multiple sclerosis (MS), but there is little data on how this molecule may affect neuroinflammation. Here, we have studied the mouse ortholog in C57BL/6 wild-type and Il22ra2-deficient mice in the context of experimental autoimmune encephalomyelitis (myelin oligodendrocyte glycoprotein-EAE). In wild-type mice, we demonstrated changes in the levels of transcripts for IL-22, the signaling IL-22 receptor and IL-22BP in lymphoid tissues at the time of T-cell priming and in the inflamed central nervous system (CNS). Because IL-22BP is known to antagonize IL-22 signaling, a primarily pro-inflammatory cytokine, we hypothesized that the Il22ra2-deficient mice would have more severe EAE. Paradoxically, the knockout mice displayed a less severe disease course, less demyelination and less infiltration of immune cells in the CNS. The most straightforward interpretation of our findings is that lack of IL-22BP leads to a higher availability of IL-22, which in the case of CNS inflammation, surprisingly acts in a protective fashion. Thus, deletion of the ortholog of the MS risk gene Il22ra2 in mice has beneficial effects on EAE, which may be considered in new therapeutic strategies for treating neuroinflammation.