Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids.

Intestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor signaling. IL-37 is an anti-inflammatory cytokine that inhibits innate signaling in diverse cells by signaling through SIGIRR. Despite the strong expression of SIGIRR by IEC, few studies have examined whether IL-37 can suppress their innate immune signaling. We characterized innate immune responses of human and murine colonoids to bacteria (FliC, LPS) and host (IL-1ß) products and the role of IL-37/SIGIRR in regulating these responses. We demonstrated that human colonoids responded only to FliC, but not to LPS or IL-1ß. While colonoids derived from different donors displayed significant inter-individual variability in the magnitude of their innate responses to FliC stimulation, all colonoids released a variety of chemokines. Interestingly, IL-37 attenuated these responses through inhibition of p38 and NFκB signaling pathways. We determined that this suppression by IL-37 was SIGIRR dependent, in murine organoids. Along with species-specific differences in IEC innate responses, we show that IL-37 can promote IEC hypo-responsiveness by suppressing inflammatory signaling.

A precipitation gradient drives change in macroinvertebrate composition and interactions within bromeliads.

Ecological communities change across spatial and environmental gradients due to (i) changes in species composition, (ii) changes in the frequency or strength of interactions or (iii) changes in the presence of the interactions. Here we use the communities of aquatic invertebrates inhabiting clusters of bromeliad phytotelms along the Brazilian coast as a model system for examining variation in multi-trophic communities. We first document the variation in the species pools of sites across a geographical climate gradient. Using the same sites, we also explored the geographic variation in species interaction strength using a Markov network approach. We found that community composition differed along a gradient of water volume within bromeliads due to the spatial turnover of some species. From the Markov network analysis, we found that the interactions of certain predators differed due to differences in bromeliad water volume. Overall, this study illustrates how a multi-trophic community can change across an environmental gradient through changes in both species and their interactions.