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BackgroundInterstitial pneumonia in connective tissue diseases (CTD-IP) featuring inflammation and fibrosis is a leading cause of death in CTD-IP patients. The related autoimmune lung injury and disturbed self-healing process make conventional anti-inflammatory drugs ineffective. Equipped with unique immunoregulatory and regenerative properties, mesenchymal stem cells (MSCs) may represent a promising therapeutic agent in CTD-IP. In this study, we aim to define the immunopathology involved in pulmonary exacerbation during autoimmunity and to determine the potential of MSCs in correcting these disorders.MethodsLung and blood specimens, bronchoalveolar lavage fluid cells collected from CTD-IP patients, and human primary lung fibroblasts (HLFs) from patients pathologically diagnosed with usual interstitial pneumonia (UIP) and healthy controls were analyzed by histology, flow cytometry and molecular biology. T cell subsets involved in the process of CTD-IP were defined, while the regulatory functions of MSCs isolated from the bone marrow of normal individuals (HBMSCs) on cytotoxic T cells and CTD-UIP HLFs were investigated in vitro.ResultsHigher frequencies of cytotoxic T cells were observed in the lung and peripheral blood of CTD-IP patients, accompanied with a reduced regulatory T cell (Treg) level. CTD-UIP HLFs secreted proinflammatory cytokines in combination with upregulation of α-smooth muscle actin (α-SMA). The addition of HBMSCs in vitro increased Tregs concomitant with reduced cytotoxic T cells in an experimental cell model with dominant cytotoxic T cells, and promoted Tregs expansion in T cell subsets from patients with idiopathic pulmonary fibrosis (IPF). HBMSCs also significantly decreased proinflammatory chemokine/cytokine expression, and blocked α-SMA activation in CTD-UIP HLFs through a TGF-β1-mediated mechanism, which modulates excessive IL-6/STAT3 signaling leading to IP-10 expression. MSCs secreting a higher level of TGF-β1 appear to have an optimal anti-fibrotic efficacy in BLM-induced pulmonary fibrosis in mice.ConclusionsImpairment of TGF-β signal transduction relevant to a persistent IL-6/STAT3 transcriptional activation contributes to reduction of Treg differentiation in CTD-IP and to myofibroblast differentiation in CTD-UIP HLFs. HBMSCs can sensitize TGF-β1 downstream signal transduction that regulates IL-6/STAT3 activation, thereby stimulating Treg expansion and facilitating anti-fibrotic IP-10 production. This may in turn block progression of lung fibrosis in autoimmunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0319-y) contains supplementary material, which is available to authorized users.

Pancreatic cancer (PC) is one of the leading causes of cancer-related deaths worldwide. Frequent metastasis and recurrence are the main reasons for the poor prognosis of PC patients. Thus, the discovery of new biomarkers and wider insights into the mechanisms involved in pancreatic tumorigenesis and metastasis is crucial. In the present study, we report that leukemia inhibitory factor receptor (LIFR) suppresses tumorigenesis and metastasis of PC cells both in vitro and in vivo. LIFR expression was significantly lower in PC tissues and was associated with local invasion (P=0.047), lymph node metastasis (P=0.014) and tumor-node-metastasis (TNM) stage (P=0.002). Overexpression of LIFR significantly suppressed PC cell colony formation (P=0.005), migration (P=0.003), invasion (P=0.010) and wound healing ability (P=0.013) in vitro, while opposing results were observed after LIFR was silenced. Furthermore, animal xenograft and metastasis models confirm that the in vivo results were consistent with the outcomes in vitro. Meanwhile, LIFR inhibited the expression of β-catenin, vimentin and slug and induced the expression of E-cadherin, suggesting that the epithelial-mesenchymal transition regulation pathway may underlie the mechanism. These results indicate that LIFR negatively regulates the metastasis of PC cells.