The epithelium-associated cytokine thymic stromal lymphopoietin (TSLP) can induce OX40L and CCL17 expression by myeloid dendritic cells (mDCs), which contributes to aberrant Th2-type immune responses. Herein, we report that such TSLP-induced Th2-type immune response can be effectively controlled by Dectin-1, a C-type lectin receptor expressed by mDCs. Dectin-1 stimulation induced STAT3 activation and decreased the transcriptional activity of p50-RelB, both of which resulted in reduced OX40L expression on TSLP-activated mDCs. Dectin-1 stimulation also suppressed TSLP-induced STAT6 activation, resulting in decreased expression of the Th2 chemoattractant CCL17. We further demonstrated that Dectin-1 activation was capable of suppressing ragweed allergen (Amb a 1)-specific Th2-type T cell response in allergy patients ex vivo and house dust mite allergen (Der p 1)-specific IgE response in non-human primates in vivo. Collectively, this study provides a molecular explanation of Dectin-1-mediated suppression of Th2-type inflammatory responses and suggests Dectin-1 as a target for controlling Th2-type inflammation.

Beta cell replacement therapy, the transplantation of isolated pancreatic islets by intraportal infusion, offers patients with brittle type 1 diabetes blood glucose regulation with a minimally invasive technique. Chemical modification of islets prior to transplantation, providing a nanothin barrier that potentially includes active protective compounds, has been proposed as a strategy to minimize the inflammatory and immune reactions that often significantly limit graft function and duration. Chemical modification also has the potential to allow the use of alternative sources of islets, such as porcine islets, for transplantation. This investigation compared three orthogonal covalent islet modification techniques across three species (human, porcine, and murine), using multiple measures to determine biocompatibility and effectiveness. All three conjugation chemistries were well tolerated, and the overall efficiency, gross uniformity, and stability of the surface modifications were dependent upon the conjugation chemistry as well as the islet source (human, porcine, or murine). Notably, the reductive modification of surface disulfides was shown to afford intense and long-lasting modification of human islets. This study demonstrates that murine, human, and porcine islets tolerate a variety of covalent modifications, that these modifications are relatively stable, and that the murine islet model may not be predictive for some chemical contexts.

On a sweltering summer morning, throngs of people filed into Jones Theatre at Baylor University in Waco for the graduate student orientation. One could look around and notice the diversity of not only the student population, but also the disciplines being represented. Many students had stepped off planes only hours prior, but even those who had been traveling for days could not contain their excitement. As for me, I was nowhere near any of this. I was still 40 miles north of Waco in Waxahachie, having been pulled over for speeding. After 4 days of traveling with my life in my Volkswagon Jetta, all the way from San Francisco, on one of the most important days of my life, I was late. When I finally arrived at the Hooper Schafer Fine Arts Auditorium, out of breath from running all the way from the parking structure, all of the graduate students were quietly listening to the first introductory speech. I snuck into the back and sat down. My mind was racing, as I knew very little about Waco and Baylor University except for the growing accomplishments of the biomedical studies program. What little I did know about Baylor seemed so different from my very liberal upbringing in California. What would this experience be like for me? But, as I listened to the talks, met with other students, and finally met the entire biomedical studies entering class of 2007, I knew that I had made the right decision in coming to Baylor. This would be an experience unlike any other, and I was wholeheartedly open to embracing it. -Christine Morel, PhD candidate, Institute of Biomedical Studies.

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