Eftychi C, Schwarzer R, Vlantis K, Wachsmuth L, Basic M, Wagle P, Neurath M, Becker C, Bleich A, Pasparakis M (2019)
Publication Type: Journal article
Publication year: 2019
Book Volume: 51
Pages Range: 367-380.e4
Journal Issue: 2
DOI: 10.1016/j.immuni.2019.06.008
Epithelial barrier defects are implicated in the pathogenesis of inflammatory bowel disease (IBD); however, the role of microbiome dysbiosis and the cytokine networks orchestrating chronic intestinal inflammation in response to barrier impairment remain poorly understood. Here, we showed that altered Schaedler flora (ASF), a benign minimal microbiota, was sufficient to trigger colitis in a mouse model of intestinal barrier impairment. Colitis development required myeloid-cell-specific adaptor protein MyD88 signaling and was orchestrated by the cytokines IL-12, IL-23, and IFN-γ. Colon inflammation was driven by IL-12 during the early stages of the disease, but as the mice aged, the pathology shifted toward an IL-23-dependent inflammatory response driving disease chronicity. These findings reveal that IL-12 and IL-23 act in a temporally distinct, biphasic manner to induce microbiota-driven chronic intestinal inflammation. Similar mechanisms might contribute to the pathogenesis of IBD particularly in patients with underlying intestinal barrier defects.
APA:
Eftychi, C., Schwarzer, R., Vlantis, K., Wachsmuth, L., Basic, M., Wagle, P.,... Pasparakis, M. (2019). Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment. Immunity, 51(2), 367-380.e4. https://doi.org/10.1016/j.immuni.2019.06.008
MLA:
Eftychi, Christina, et al. "Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment." Immunity 51.2 (2019): 367-380.e4.
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