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Leonie Hussaarts Department of Parasitology, Leiden Immunoparasitology Group Leiden University Medical Center, Leiden, Netherlands Keystone – Type 2 Immunity: Initiation, Maintenance, Homeostasis and Pathology From January 10 to January 15, Santa Fe (New Mexico, USA) was the scientific hub for investigators of type 2 immune responses. The Keystone conference on Type 2 Immunity was held jointly with another Keystone meeting: “Pathogenic Processes in Asthma and COPD”. During the 4.5 day program, participants could attend lectures of both meetings, and were encouraged to interact during the poster sessions, over meals or during the social hours. The lectures of the conference on Type 2 Immunity focused on the major advances in the field, and covered a wide range of topics: Type 2 immune responses were discussed in the context of helminth infection, wound repair or commensal bacteria, and lectures focused on both adaptive and innate immune cells and their cytokines. The session I found most interesting was dedicated to the recently discovered type 2 innate lymphoid cells (ILC2s). The speakers gave a great overview of this expanding area of research. The field is relatively young, so I found it fascinating to learn that it has clearly been established that ILC2s play an important role in both the initiation and amplification of type 2 immune responses. Participants who were not selected for an oral presentation, could showcase a poster during one of the three poster sessions. Each session contained posters of both meetings, adding up to about 50 posters per session. During these informal sessions, I exchanged ideas with researchers interested in topics similar to that of my own PhD project. I presented my own data during the second session. It was a great experience to discuss my findings extensively with both senior scientists and graduate students. Overall, the conference was inspiring and provided an excellent overview of the state of the art in the field of type 2 immune responses. The informal atmosphere during the poster sessions and social hours provided a great opportunity to meet (established) researchers. I would like to thank the NVP for the financial contribution. Rapamycin and helminth antigens: mTOR-dependent and -independent mechanisms to condition human dendritic cells for Th2 polarization 1 1 2 1 3 1 L Hussaarts , HH Smits , G Schramm , AJ van der Ham , GCM van der Zon , H Haas , B Guigas 1 and M Yazdanbakhsh 1 Dept. of Parasitology, LUMC, The Netherlands 2 Research Center Borstel, Germany 3 Dept. of Molecular Cell Biology, LUMC, The Netherlands 1,3 Recent reports have attributed an immunoregulatory role to the mammalian target of rapamycin (mTOR), a key protein kinase integrating input from growth factors and nutrients to promote cell growth and division. Since the mechanisms driving T helper 2 (Th2) polarization remain poorly understood, we investigated the role of the mTOR pathway in Th2 skewing by dendritic cells (DC). + Using a co-culture system of human monocyte-derived LPS-matured DC and allogeneic naïve CD4 T cells, we show that blocking mTOR with the immunosuppressive drug rapamycin reduced the expression of CD86, CD80 and HLA-DR on DC, and promoted Th2 skewing characterized by increased IL-4 and decreased IFN-γ levels. We next investigated whether antigens from helminth parasites, the strongest natural inducers of Th2 responses, affect the mTOR pathway. To this end, we used Schistosoma mansoni soluble egg antigen (SEA) and omega-1, which is a single molecule recently identified as the major component in SEA responsible for Th2 skewing. Importantly, in contrast to rapamycin, neither SEA nor omega-1 reduced the phosphorylation of mTOR’s downstream targets P70S6 kinase and 4EBP1, suggesting that these antigens do not affect the pathway. In addition, co-stimulation with SEA and rapamycin promoted a stronger Th2 response than stimulation with either SEA or rapamycin alone, further supporting the existence of two independent mechanisms for Th2 polarization. We conclude that conditioning human DC to skew immune responses towards Th2 can be achieved via an mTOR-dependent and an mTOR-independent pathway by rapamycin and helminth antigens, respectively. These findings contribute to the understanding of the different modes and mechanisms by which DC can be accurately modulated for clinical use. Grant support: EU IDEA (HEALTH-F3-2009-241642) Rapamycin and helminth antigens: mTOR-dependent and -independent mechanisms to condition human dendritic cells for Th2 polarization 1 1 2 1 3 1 L Hussaarts , HH Smits , G Schramm , AJ van der Ham , GCM van der Zon , H Haas , B Guigas 1 and M Yazdanbakhsh 1 Dept. of Parasitology, LUMC, The Netherlands 2 Research Center Borstel, Germany 3 Dept. of Molecular Cell Biology, LUMC, The Netherlands 1,3 Recent reports have attributed an immunoregulatory role to the mammalian target of rapamycin (mTOR), a key protein kinase integrating input from growth factors and nutrients to promote cell growth and division. Since the mechanisms driving T helper 2 (Th2) polarization remain poorly understood, we investigated the role of the mTOR pathway in Th2 skewing by dendritic cells (DC). + Using a co-culture system of human monocyte-derived LPS-matured DC and allogeneic naïve CD4 T cells, we show that blocking mTOR with the immunosuppressive drug rapamycin reduced the expression of CD86, CD80 and HLA-DR on DC, and promoted Th2 skewing characterized by increased IL-4 and decreased IFN-γ levels. We next investigated whether antigens from helminth parasites, the strongest natural inducers of Th2 responses, affect the mTOR pathway. To this end, we used Schistosoma mansoni soluble egg antigen (SEA) and omega-1, which is a single molecule recently identified as the major component in SEA responsible for Th2 skewing. Importantly, in contrast to rapamycin, neither SEA nor omega-1 reduced the phosphorylation of mTOR’s downstream targets P70S6 kinase and 4EBP1, suggesting that these antigens do not affect the pathway. In addition, co-stimulation with SEA and rapamycin promoted a stronger Th2 response than stimulation with either SEA or rapamycin alone, further supporting the existence of two independent mechanisms for Th2 polarization. We conclude that conditioning human DC to skew immune responses towards Th2 can be achieved via an mTOR-dependent and an mTOR-independent pathway by rapamycin and helminth antigens, respectively. These findings contribute to the understanding of the different modes and mechanisms by which DC can be accurately modulated for clinical use.