Here, we report that hCG regulates the SIRT1/FOXO3a axis in hepatocytes, resulting in immune suppression by attenuating caspase-3-dependent IL-16 processing and release, which concomitantly prevents autoaggressive T-cell infiltration of the liver. Considering the low toxicity profile of hCG in humans, interrupting the inflammatory cycle by hCG opens new perspectives for therapeutic intervention of inflammatory liver diseases. (Hepatology 2017;65:2074-2089).

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Asthma is caused by T-helper 2 (Th2)-driven immune-responses in which upregulation of GATA-3 has been shown to play a crucial role in both in humans and in murine models of this disease. T-cell tolerance, induced by respiratory exposure to allergen prior to allergen sensitization, can inhibit the development of airway hyperractivity (AHR), a cardinal feature of asthma. However, the subset of T cells that mediates this protective function in allergic asthma has not been clearly identified yet. We recently set up a tolerogenic model of allergic asthma. In this model, peripheral T cell tolerance is induced by respiratory exposure to allergen and is characterized by decreased Th2 (IL-4,IL-5 and IL-13)-based responses via downregulation of the main Th2 transcription factor GATA-3 in the lung which results in decreased allergen induced AHR and lung eosinophilia. In addition, we found that our tolerogenic model is characterized also by decreased differentiation of Th17 cells. Moreover respiratory exposure to allergen prior to sensitization protected also airway hyperreactivity induced in the absence of T-bet. Thus this model suppressed effector Th2 and Th17 mediated immune responses also in the absence of IFN-gamma and could therefore provide a new avenue also for genetically determined allergic diseases. This work is supported by a SFB 548-B8 project in Mainz, Germany

The transforming growth factor beta TGFβ is known to be a potent tumour suppressor at early stages of cancer. However, cancer cells can lose responsiveness to TGFβ through mutations in the signaling pathway downstream of the TGFβ receptor. TGFβ influences the development of regulatory T cells known to enhance cancer development. We analyzed TGFβ expression in the lung of subjects affected by lung adenocarcinoma. TGFβ mRNA level was increased in the lung of these patients and this value correlated with the progression of the disease. We thus asked whether targeting TGFβ signalling in T cells would inhibit regulatory T cells in a murine model of lung adenocarcinoma. Mice that overexpress a dominant negative form of TGFβ type II receptor lacking the cytoplasmic kinase domain in T cells were used. Histologically, we found a tumour regression in the abscence of TGFβ signalling in T cells. A hyperproliferation of the CD4+ T cells overproducing interferon gamma (IFNγ) was observed. Analysis of the regulatory T cells showed an intact supression function of these cells. In summary, a defective TGFβ-signalling in lung T cells could lead to amelioration of lung adenocarcinoma in mice because inducing hyperproliferation of IFN-gamma producing CD4+ T cells thus limiting the T regulatory component in this disease. This work is supported by the GK1043 in Mainz.

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