Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment

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

Journal

Immunity Elsevier

Book Volume: 51

Pages Range: 367-380.e4

Journal Issue: 2

DOI: 10.1016/j.immuni.2019.06.008

Abstract

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.

Authors with CRIS profile

Markus Neurath Lehrstuhl für Innere Medizin I Christoph Becker Professur für Molekulare Gastroenterologie

Involved external institutions

Universität zu Köln DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

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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