Tissue-resident macrophages (TMs), including epidermal Langerhans cells (LCs), are long-lived cells able to proliferate. Their ontogeny and adaptation to different organs have been studied in great details, yet knowledge about the cellular factors allowing their physiological maintenance deserves further investigations. Autophagy, a catabolic process regulated by autophagy-related (Atg) genes, prevents accumulation of harmful cytoplasmic components particularly in long-lived and self-renewing cells, and mobilizes energetic reserve in certain cellular or physiological contexts. Recently, we found that Atg5-deficient LCs undergo apoptosis as a result of lipid metabolism dysregulation. Here, we propose that autophagy allows TMs to manage lipid stocks and ensure long-term maintenance. We also anticipate that autophagy modulation impacts the regulation of inflammatory activity of TMs. We will first validate this in murine and human LCs, then verify whether it holds true for TMs of the lung, liver and lymph nodes. Finally, we will test whether autophagy could permit TMs to adapt to cellular stress and limit inflammation induced by metabolic alterations, irradiation, aging and viral infection. Altogether, our results will introduce a new paradigm on the maintenance of TMs in a broad range of organs under physiological and inflammatory conditions.
The host team will mainly study TMs of the skin and lymph nodes. The subject requires to work on animal models (genetically modified mice, CRE/lox models) as well as on skin samples from patients. The candidate must have a good knowledge of immunology, experience in cell culture (immune cells, primary cells) and be familiar with the required analytical techniques (RT-PCR, immunohistochemistry, flow cytometry, ELISA). Since transcriptomic and metabolomic analyses are planned, training in bioinformatics would be an asset. The student will be trained in basic and applied immunology and dermatology.
In your work, you demonstrate dynamism and reactivity and you appreciate teamwork. You are rigorous, organized and methodical. A good team spirit and good communication skills are required to improve productivity and ensure the achievement of objectives.
English read/write necessary (international team, protocols written in English).
Keywords : Immunology, Inflammation, Dendritic cells, Macrophages, Skin, Lymph nodes, Metabolism
This PhD will be carried out in Dr. Christopher Mueller’s team “Immune-microenvironment interactions in health and disease”. Our research aims to study the interactions ensuring the adaptation of the immune system to its environment and to the surrounding cells (fibroblasts, endothelium, neurons…). At present, the dynamic and international team is composed of 2 researchers, 2 ITA, 2 PhD students and 3 post-doctoral fellows. The project funded by the National Research Agency is based on a collaboration with Dr. Frédéric Gros (UMR 1109 INSERM, Biomedicine Research Center of Strasbourg), who will be co-director of the PhD student.