Control of GM-CSF-Dependent Dendritic Cell Differentiation and Maturation by DEF6 and SWAP-70.

Although GM-CSF has been widely used in dendritic cell (DC) research, the mechanisms, factors, and signals regulating steady-state differentiation and maturation of GM-CSF-dependent DCs are insufficiently known. We found that the absence, individually or combined, of the related proteins DEF6 and SWAP-70 strongly enhances differentiation of murine GM-CSF-derived DCs. Contrasting SWAP-70, control through DEF6 does not depend on RHOA activation. DEF6 deficiency leads to expression of the DC-specific transcription factor ZBTB46 and prolonged STAT5 activation in GM-CSF cultures. SWAP-70 and DEF6-mediated restriction of DC differentiation converges mechanistically at the NF-κB pathway. DEF6 acts at early stages of DC differentiation in CD115-cKIT+ myeloid DC progenitors, whereas SWAP-70 acts subsequently. SWAP-70 and DEF6 regulate steady-state DC cytokine expression as well as in vivo accumulation in lymphatic tissue of migratory DCs. Our studies thus elucidate previously unknown roles of two closely related factors with distinct and complementary activities in DC differentiation and steady-state DC function.

[Climate protection in practices - current status, motivation and challenges in outpatient care]. / Klimaschutz in der Praxis ­ Status quo, Bereitschaft und Herausforderungen in der ambulanten Versorgung.

INTRODUCTION: The impact of climate change on health and the necessity to reduce emissions in the health sector is becoming an increasingly discussed topic. Little is known about medical doctors' (MDs) attitude towards climate protection measures in outpatient practices. METHODS: Between October 2020 and February 2021, a survey was conducted among MDs in German practices. 1,683 participants answered 39 questions on energy use, transportation, disposable materials, budget and patient counselling. Data were collected on status, motivation, obstacles and needs regarding climate protection in practices. RESULTS: 83% considered climate change an urgent problem requiring immediate action. A majority reported climate effects on their patients' health. Most MDs felt responsible for climate protection in their practices, showing a high degree of willingness to implement climate-friendly measures. Obstacles reported include lack of information and institutional support as well as the expected financial burden. A majority of MDs called on professional associations and politics to develop climate-friendly strategies. CONCLUSION: In view of national climate targets and the willingness of outpatient MDs to contribute to climate protection, support from medical associations is required, e. g. through practical recommendations and financial help, in order to transform the health sector in accordance with the idea of Planetary Health. Accompanying studies should provide further evidence on effective measures to reduce greenhouse gas emissions in practices.