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Arrested alveolar development is the main pathological characteristic of neonatal bronchopulmonary dysplasia (BPD); however, a number of studies aiming to improve alveolarization have focused on alveolar epithelial cell damage and impairment. Previously, the authors reported that the Wnt signaling plays a key role in alveolar injury and repair by regulating alveolar epithelial type II cell (AECII) proliferation and differentiation. In the present study, the authors wished to investigate whether Yes-associated protein (YAP), a transcriptional coactivator in the Hippo signaling pathway, affects AECII proliferation and differentiation via the Wnt/β-catenin pathway in BPD. It was found that YAP regulated AECII proliferation and differentiation. A decreased expression of YAP, Wnt3a and nuclear β-catenin was observed in lung tissues affected by BPD. In vitro , YAP and Wnt3a overexpression in BPD promoted AECII proliferation and differentiation into AECIs by increasing the nuclear transfer of β-catenin and vice versa. The effects of a decreased Wnt3a expression in primary AECIIs in BPD were compensated by YAP overexpression, as were the effects of Wnt3a knockdown in primary AECIIs. On the whole, the findings of the present study demonstrate that YAP and Wnt3a independently promote AECII proliferation and differentiation in experimental BPD by increasing the nuclear β-catenin levels. Therefore, Wnt3a or YAP may be candidate regulatory targets for improving the outcomes of BPD.

Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive secretion of type I interferon in response to foreign nuclei acids. Combined with their antigen presentation capacity, this powerful functionality enables pDCs to orchestrate innate and adaptive immune responses. Cholecystokinin octapeptide (CCK8) is a potent immunomodulator, whose role in pDCs function is unknown. In this study, we found that two different cholecystokinin receptors, CCK1R and CCK2R, are expressed on human peripheral blood pDCs. Exogenous CCK8 was able to modulate the TLR-induced activation of pDCs, including phenotypic maturation, IFN-α synthesis and secretion, and could also regulate the potential of pDCs to induce adaptive immune responses in vitro. CCK8 inhibited TLR9-induced activation of tumor-necrosis factor receptor-associated factor 6, which is an important adapter protein in activation of interferon-regulatory factor (IRF)5 and IRF7, possibly through CCK2R, by evoking the activity of protein kinase (PK)A and reducing the activity of PKC. All these results indicate that CCK8 can inhibit the TLR9-induced phenotypic maturation and activation of pDCs, acting through CCK2R by modulating the tumor-necrosis factor receptor-associated factor 6 signaling pathways. Keywords: CCK8 · IFN-α · IRF7 · Plasmacytoid dendritic cells · TRAF6Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionTwo naturally occurring DC types have been described in human peripheral blood: plasmacytoid dendritic cells (pDCs)/professional type I interferon-producing cells and classical dendritic cells (cDCs)/myeloid DCs [1,2]. pDCs are considered the main sentinels against viral infections and play a major role in immune tolerance [3]. This function of pDCs is linked to their expression of TLR7 and TLR9, both of which sense viral nucleic acids within the early endosomes [4,5]. TLR9 is only expressed by Correspondence: Prof. Bin Cong e-mail: hbydbincong@126.com pDCs in the human setting and is responsible for a very high type I IFN response. Tumor necrosis factor-associated factor 6 (TRAF6) is critical for mediating TLR signaling and subsequent activation of interferon-regulatory factor (IRF) 5 and IRF7, transcriptional activators of innate immunity [6].An increasing amount of data supports the idea that the nervous, endocrine, and immune systems are closely interconnected and that they mutually influence their respective functions through common mediators and receptors. It is known that some neuropeptides, namely vasoactive intestinal peptide and somatostatin, inhibit the proliferative response of lymphocytes [7,8]. Members of the cholecystokinin (CCK)/gastrin family of peptides play an important role in the regulation of feeding behavior and energy homeostasis [9]. CCK is identified as several different forms C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 490Xianxian Jia et al. Eur. J. Immunol. 2014. 44: 489-499 of the peptide with different sizes, includ...

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