Projects Offered

1 PhD project offered in the IPP winter call Molecular Biomedicine & Ageing

Scientific Background

Dendritic cells in the skin perform diverse functions. Acting primarily as sentinel cells, they form a critical bridge between the innate and adaptive immune system. Their ability to detect and respond to virtually all pathogens ensures rapid immune activation, while also modulating longer-term immune responses. Specifically, they play key roles in pathogen recognition, antigen uptake, processing and presentation, but also contribute to tissue homeostasis, tolerance to commensal microbes and wound healing. To carry out these diverse and complex tasks efficiently, dendritic cells have evolved into specialized subsets, each characterized by distinct phenotypic and functional properties, as well as distinct activation and interaction potentials and localization.

Thus, type 1 dendritic cells are known to cross-present antigens and activate CD8 T cell responses, Langerhans Cells are associated with Tolerance and homeostasis, plasmacytoid DC contribute to the defense against viruses, while type 2 dendritic cells drive CD4+ T helper cell differentiation, influencing the balance of Th1, Th2 or Th17 immune responses. 

Recent advances in single cell profiling have identified additional Dendritic cell populations, including transitional tDC and type 3 Dendritic cells. Yet, their functional role in tissues is incompletely understood. We hypothesize that these Dendritic cells have a unique functional profile and are located within defined locations within the skin to facilitate specialized interactions. Understanding type 3 dendritic cells biology in the context of health and disease will allow us to develop targeted therapeutic strategies aimed at modulating their activity for improved clinical outcomes.

PhD project: Type 3 Dendritic cell immunology and functionality in the skin

In our previous work we have developed a number of tools to study skin dendritic cells on a single cell level. This includes single-cell RNAseq datasets and analysis tools, large high-dimensional flow cytometry phenotyping panels and a collection of transgenic mouse models specifically engineered for the reporting, lineage tracing, or conditional deletion of defined dendritic cell subsets, providing powerful genetic tools for dissecting cell-specific roles in vivo. Using and optimizing these tools to study Type 3 Dendritic cells in mouse models of health and disease will be critical to characterize their unique biology and location. This work will be essential for elucidating their functional role in skin immunity and homeostasis, and evaluating their therapeutic potential in modulating immune responses in dermatological diseases.

This PhD requires a strong background in immunology, previous experience with the complex phenotyping of immune cells and proficiency in working with in vivo animal models, including handling, experimental design and tissue sampling.

If you are interested in this project, please select Mayer (DC3) as your project preference in the IPP application platform.

Publications relevant to this project

Mayer JU, Hilligan KL, Chandler JS, Eccles DA, Old SI, Domingues RG, Yang J, Webb GR, Munoz-Erazo L, Hyde EJ, Wakelin KA, Tang SC, Chappell SC, von Daake S, Brombacher F, Mackay CR, Sher A, Tussiwand R, Connor LM, Ortega DG, Jankovic D, Gros GL, Hepworth MR, Lamiable O, Ronchese F (2021) Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization. Nat. Immunol., 1 (13). Link

Sheng J, Chen Q, Wu X, Dong YW, Mayer J, Zhang J, Wang L, Bai X, Liang T, Sung YH, Goh WWB, Ronchese F, Ruedl C. (2021) Fate Mapping Analysis Reveals a Novel Murine Dermal Migratory Langerhans-like Cell Population. eLife, 10, e65412.Link

Hilligan KL, Tang SC, Hyde EJ, Roussel E, Mayer JU, Yang J, Wakelin KA, Schmidt AJ, Connor LM, Sher A, MacDonald AS, Ronchese F. (2020) Dermal IRF4+ Dendritic Cells and Monocytes License CD4+ T Helper Cells to Distinct Cytokine Profiles. Nat. Commun., 11 (1), 5637.Link

Liu Z, Wang H, Li Z, Dress RJ, Zhu Y, Zhang S, De Feo D, Kong WT, Cai P, Shin A, Piot C, Yu J, Gu Y, Zhang M, Gao C, Chen L, Wang H, Vétillard M, Guermonprez P, Kwok I, Ng LG, Chakarov S, Schlitzer A, Becher B, Dutertre CA, Su B, Ginhoux F. (2023) Dendritic cell type 3 arises from Ly6C+ monocyte-dendritic cell progenitors. Immunity. Aug 8;56(8):1761-1777.e6. Link