|
Journal Club 01 IL-23–producing IL-10R–deficient gut macrophages elicit an IL-22–driven proinflammatory epithelial cell response  Bernshtein B1, Curato C1, Ioannou M2, Thaiss CA1, Gross-Vered M1, Kolesnikov M1, Wang Q2, David E1, Chappell-Maor L1, Harmelin A3, Elinav E1, Thakker P4, Papayannopoulos V2, Jung S5. Sci Immunol. 2019 Cytokines maintain intestinal health, but precise intercellular communication networks remain poorly understood. Macrophages are immune sentinels of the intestinal tissue and are critical for gut homeostasis. Here, we show that in a murine inflammatory bowel disease (IBD) model based on macrophage-restricted interleukin-10 (IL-10) receptor deficiency (Cx3cr1Cre: Il10rafl/fl mice), proinflammatory mutant gut macrophages cause severe spontaneous colitis resembling the condition observed in children carrying IL-10R mutations. The research team established macrophage-derived IL-23 as the driving factor of this pathology. Specifically, they reported that Cx3cr1Cre: Il10rafl/fl: Il23afl/fl mice harboring macrophages deficient for both IL-10R and IL-23 are protected from colitis. By analyzing the epithelial response to proinflammatory macrophages, they provided evidence that T cells of colitic animals produce IL-22, which induces epithelial chemokine expression and detrimental neutrophil recruitment. Collectively, the scientists defined macrophage-specific contributions to the induction and pathogenesis of colitis, as manifested in mice harboring IL-10R deficiencies and human IBDs https://immunology./content/4/36/eaau6571 02 IFN-I and IL-22 mediate protective effects of intestinal viral infection  Neil JA1, Matsuzawa-Ishimoto Y1, Kernbauer-Hölzl E1, Schuster SL1, Sota S1,2, Venzon M1,2, Dallari S1, Galvao Neto A3, Hine A4,5, Hudesman D5, Loke P4, Nice TJ6, Cadwell K7,8. Nat Microbiol. 2019 Products derived from bacterial members of the gut microbiota evoke immune signaling pathways of the host that promote immunity and barrier function in the intestine. How immune reactions to enteric viruses support intestinal homeostasis is unknown. The researchers recently demonstrated that infection by murine norovirus (MNV) reverses intestinal abnormalities following depletion of bacteria, indicating that an intestinal animal virus can provide cues to the host that are typically attributed to the microbiota. Here, they elucidated mechanisms by which MNV evokes protective responses from the host. They identified an important role for the viral protein NS1/2 in establishing local replication and a type I interferon (IFN-I)response in the colon. They further showed that IFN-I acts on intestinal epithelial cells to increase the proportion of CCR2-dependent macrophages and interleukin (IL)-22-producing innate lymphoid cells, which in turn promotepSTAT3 signaling in intestinal epithelial cells and protection from intestinal injury. In addition, they demonstrated that MNV provides striking IL-22-dependent protection against early-life lethal infection by Citrobacter rodentium. These findings demonstrated novel ways in which a vital member of the microbiota fortifies the intestinal barrier during chemical injury and infectious challenges. https://www./articles/s41564-019-0470-1 Edited by Qianru Huang |
|
|
