Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic forms of inflammatory bowel disease. The behavior of these diseases varies unpredictably among patients. Identification of reliable prognostic biomarkers would enable treatment to be personalized so that patients destined to experience aggressive disease could receive appropriately potent therapies from diagnosis, while those who will experience more indolent disease are not exposed to the risks and side effects of unnecessary immunosuppression. Using transcriptional profiling of circulating T cells isolated from patients with CD and UC, we identified analogous CD8 + T cell transcriptional signatures that divided patients into 2 otherwise indistinguishable subgroups. In both UC and CD, patients in these subgroups subsequently experienced very different disease courses. A substantially higher incidence of frequently relapsing disease was experienced by those patients in the subgroup defined by elevated expression of genes involved in antigen-dependent T cell responses, including signaling initiated by both IL-7 and TCR ligation -pathways previously associated with prognosis in unrelated autoimmune diseases. No equivalent correlation was observed with CD4 + T cell gene expression. This suggests that the course of otherwise distinct autoimmune and inflammatory conditions may be influenced by common pathways and identifies what we believe to be the first biomarker that can predict prognosis in both UC and CD from diagnosis, a major step toward personalized therapy.

Genetic adaptation, occurring over a long evolutionary time, enables host-specialized herbivores to develop novel resistance traits and to efficiently counteract the defenses of a narrow range of host plants. In contrast, physiological acclimation, leading to the suppression and/or detoxification of host defenses, is hypothesized to enable broad-generalists to shift between plant hosts. However, the host adaptation mechanisms used by generalists composed of host-adapted populations are not known. Two-spotted spider mite (Tetranychus urticae) is an extreme generalist herbivore whose individual populations perform well only on a subset of potential hosts. We combined experimental evolution, Arabidopsis thaliana genetics, mite reverse genetics, and pharmacological approaches to examine mite host adaptation upon the shift of a bean (Phaseolus vulgaris)-adapted population to Arabidopsis. We showed that cytochrome P450 monooxygenases are required for mite adaptation to Arabidopsis. We identified activities of two tiers of P450s: general xenobiotic-responsive P450s that have a limited contribution to mite adaptation to Arabidopsis and adaptation-associated P450s that efficiently counteract Arabidopsis defenses. In ∼25 generations of mite selection on Arabidopsis plants, mites evolved highly efficient detoxification-based adaptation, characteristic of specialist herbivores. This demonstrates that specialization to plant resistance traits can occur within the ecological timescale, enabling the two-spotted spider mite to shift to novel plant hosts.

Classification: Biological Sciences, Evolutionary Biology 1 2The generalist herbivore Tetranychus urticae (Koch) adapts to novel plant hosts through rapid 3 evolution of metabolic resistance 4 5Abstract 20Genetic adaptation, occurring over long evolutionary time, enables host-specialized herbivores 21to develop novel resistance traits and to counteract the defenses of a narrow range of host 22plants. In contrast, physiological acclimation, leading to the suppression and/or detoxification of 23 host defenses is hypothesized to enable generalists to shift between plant hosts. Here, we 24 examined the long-term response of an extreme generalist, the two-spotted spider mite, 25Tetranychus urticae Koch (TSSM), to the shift to the non-preferred and novel host plant 26Arabidopsis thaliana. We identified the key requirement of two tiers of cytochrome P450 27 monooxygenases for TSSM adaptation to Arabidopsis: general xenobiotic-responsive P450s that 28 have a limited contribution to mite adaptation to Arabidopsis and adaptation-associated P450s 29 that efficiently counteract Arabidopsis defenses, illustrating that in about 25 generations of 30 TSSM selection on Arabidopsis plants mites evolved metabolic resistances characteristic of both 31 generalist and specialist herbivores. 32 33