IL-5 and GM-CSF were determined in supernatants using specific ELISA

Kit assays (eBiosciences). The results are expressed as the mean±SD. Data were analyzed using Student’s t-test (Prism selleck chemicals GraphPad Software, San Diego, CA, USA). This work was supported by grants from the Italian Ministry of Health, Associazione Italiana Ricerca sul Cancro, Ministero dell’Istruzione, Università e Ricerca (PRIN 2005), Fondazione Cariplo, Agenzia Spaziale Italiana (Progetto OSMA), LR.26 del Friuli Venezia Giulia. The authors thank Silvia Piconese and Mario Colombo (Istituto Tumori, Milan, Italy) for providing OX40-deficient Tregs. They are grateful to Francesco Vitrani for helpful suggestions. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance anti-CTLA-4 antibody to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted

by the authors. “
“Interleukin-19 (IL-19) plays an important role in asthma by stimulating T helper type 2 (Th2) cytokine production. Interestingly, IL-4, a key Th2 cytokine, in turn up-regulates IL-19 expression in bronchial epithelial cells, so forming a positive feedback loop. In atopic dermatitis (AD), another Th2 disease closely related to asthma, IL-19 is up-regulated in the skin. We propose to use IL-4 transgenic (Tg) mice and human keratinocyte culture to delineate the molecular mechanisms involved in the up-regulation

of IL-19 in AD. IL-19 is similarly up-regulated in the skin of IL-4 Tg mice as in human AD. O-methylated flavonoid Next we show that IL-4 up-regulates IL-19 expression in keratinocytes. Interestingly, the up-regulation was suppressed by a pan-Janus kinase (Jak) inhibitor, suggesting that the Jak–signal transducer and activator of transcription (Jak-STAT) pathway may be involved. Dominant negative studies further indicate that STAT6, but not other STATs, mediates the up-regulation. Serial 5′ deletion of the IL-19 promoter and mutagenesis studies demonstrate that IL-4 up-regulation of IL-19 in keratinocytes involves two imperfect STAT6 response elements. Finally, chromatin immunoprecipitation assay studies indicate that IL-4 increases the binding of STAT6 to its response elements in the IL-19 promoter. Taken together, we delineate the detailed molecular pathway for IL-4 up-regulation of IL-19 in keratinocytes, which may play an important role in AD pathogenesis. “
“The in vivo or in vitro formation of IgG4 hybrid molecules, wherein the immunoglobulins have exchanged half molecules, has previously been reported under experimental conditions. Here we estimate the incidence of polyclonal IgG4 hybrids in normal human serum and comment on the existence of IgG4 molecules with different immunoglobulin light chains.