@ARTICLE{10.3389/fimmu.2021.810602, AUTHOR={Ritter, Kristina and Rousseau, Jasmin and Hölscher, Christoph}, TITLE={Interleukin-27 in Tuberculosis: A Sheep in Wolf’s Clothing?}, JOURNAL={Frontiers in Immunology}, VOLUME={12}, YEAR={2022}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2021.810602}, DOI={10.3389/fimmu.2021.810602}, ISSN={1664-3224}, ABSTRACT={In tuberculosis (TB), protective inflammatory immune responses and the pathological sequelae of chronic inflammation significantly depend on a timely balance of cytokine expression. In contrast to other anti-inflammatory cytokines, interleukin (IL)-27 has fundamental effects in experimental Mycobacterium tuberculosis (Mtb) infection: the absence of IL-27-mediated signalling promotes a better control of mycobacterial growth on the one hand side but also leads to a chronic hyperinflammation and immunopathology later during infection. Hence, in the context of novel host-directed therapeutic approaches and vaccination strategies for the management of TB, the timely restricted blockade of IL-27 signalling may represent an advanced treatment option. In contrast, administration of IL-27 itself may allow to treat the immunopathological consequences of chronic TB. In both cases, a better knowledge of the cell type-specific and kinetic effects of IL-27 after Mtb infection is essential. This review summarizes IL-27-mediated mechanisms affecting protection and immunopathology in TB and discusses possible therapeutic applications.} }