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Nowarski, R., Jackson, R., & Flavell, R. A. (2017). The Stromal Intervention: Regulation of Immunity and Inflammation at the Epithelial-Mesenchymal Barrier. Cell, 168(3), 362–375. Added by: Dr. Enrique Feoli (25/08/2025, 01:24) Last edited by: Dr. Enrique Feoli (25/08/2025, 17:50) |
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| Resource type: Journal Article ID no. (ISBN etc.): 928674 BibTeX citation key: Nowarski2017 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Perivascular microenvironment Keywords: barrier, epithelial, goblet, immune, immunity, inflammation, intestinal, mesenchymal, microbiota, stromal Creators: Flavell, Jackson, Nowarski Collection: Cell |
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| Abstract |
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The mesenchymal immunomodulatory capacity not only substantiates the role of tissue mesenchymal cells in the initiation of immune responses, but also places mesenchymal cells at the junction of reparative and pathological inflammation (Figure 3). Reparative inflammation depicts inflammatory signaling that mediates activation of both epithelial and connective tissue progenitors to promote expansion of the tissue structural components (Karin and Clevers, 2016). As a result of chronic injury or inflammation, however, excessive activation of fibroblasts and myofibroblasts may lead to accumulation of collagen-rich ECM and result in fibrosis. Many of the signals that induce fibroblast activation originate in damaged epithelium and include direct immune modulators such as TGF-β, IL-1, transglutaminase 2 (TG-2), and TNF, as well as immune modulators that act indirectly through immune cell activation, such as TSLP, IL-25, and IL-33 (Wynn and Ramalingam, 2012). TGF-β is expressed by multiple cell types during inflammation and is one of the most prominent drivers of fibrosis. In a multitude of organs, including the lung and kidney, the pathology mediated by TGF-β involves local fibroblast mobilization, proliferation, and differentiation into active ECM-secreting myofibroblasts, as well as recruitment of pericytes, fibrocytes, and inflammatory hematopoietic cells, resulting in excessive ECM deposition and inflammation. In the case of antigen-driven pulmonary inflammation, epithelial TGF-β promotes COX2 production in lung fibroblasts, which exacerbates chronic airway inflammation by inducing fibroblast proliferation and collagen generation, as well as mucus secretion (Sun et al., 2015). Lung injury also promotes IL-1α production by damaged AECs, which can induce inflammatory cytokines and chemokines in lung fibroblasts and promote neutrophilia and collagen deposition, exacerbating inflammatory tissue damage (Suwara et al., 2014). Induction of TG-2 signaling in alveolar epithelial cells and fibroblasts following lung injury leads to epithelial IL-6 production and activation of inflammatory responses associated with increased Th17 differentiation and fibrosis (Oh et al., 2011).
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |