GSE98850 Ribosomal Oxygenase 2 Constrains A Latent Anthelmintic Pathway In Intestinal Epithelial Cells

Contributors : Meenu R Pillai ; Belgacem Mihi ; Kenji Ishiwata ; Kiminori Nakamura ; Naoya Sakuragi ; David B Finkelstein ; Toshinori Nakayama ; Tokiyoshi Ayabe ; Peter J Ratcliffe ; Mathew L Coleman ; Mark BixSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusExpulsion of parasitic gastrointestinal nematodes requires diverse effector mechanisms coordinated by a Th2-type response. The evolutionarily conserved JmjC protein ribosomal oxygenase 2 (Riox2, formerly Mina) has been shown to repress IL4, a key Th2 cytokine, suggesting Riox2 may negatively regulate parasite expulsion. Here we report that expulsion of parasitic nematodes was indeed accelerated in Riox2 deficient mice. Unexpectedly, this was associated not with an elevated Th2 but rather an impaired Th1-type response. Further, in vitro T cell differentiation, reciprocal bone marrow chimera and conditional KO experiments demonstrated that retarded parasite expulsion and a normal Th1-type response both required Riox2 in intestinal epithelial cells (IECs). Gene profiling experiments in IECs revealed anti-microbial α-defensin peptides to be the major target of Riox2-dependent repression. In vitro exposure to recombinant α-defensin peptides caused cytotoxic damage to whipworms. These results identify a latent IEC-intrinsic anthelmintic pathway actively constrained by Riox2 and point to α-defensins as importa nt effectors that together with Riox2 would be attractive therapeutic ta...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research