Projects Offered

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

Scientific Background

Type 2 immune responses play an important role in the defense against parasites, effective wound healing and protection against toxins. Type 2 immune responses have however also been associated with detrimental immunity such as allergy and the suppression and reprogramming of proinflammatory pathways. Type 2 associated immunity has also been described within the tumor microenvironment, leading to ineffective tumor killing. Within the skin many of these responses are constantly active, correlating with an enhanced risk of allergy development and opportunistic infections that benefit from a type 2 immune bias in this tissue.

Dendritic cells play a fundamental role in the priming of T cell responses. Several lineages of dendritic cells have been described, which perform enhanced roles for certain immune responses, as cDC1 preferentially control CD8 T cell responses via cross-presentation, while cDC2 are specialized in driving different T helper cell responses by producing key molecules for their differentiation. For priming of type 2 immune responses, it is still debated if specific molecular signals for their differentiation are required or if Th2 programs develop in the absence of classical activation cytokines. Our own research has identified a unique population of dermal dendritic cells that promote enhanced type 2 immune responses within the skin. Upon activation by parasite antigens this subset of CD11b-low dermal DC2 rapidly migrates to the draining lymph nodes to activate T cells via antigen presentation, costimulatory marker expression and cytokine production. 

PhD Project: Dendritic cell bias in skin infection and cancer

In this PhD project we want to understand if skin-specific subsets of dermal DC are also involved in driving detrimental type 2 immunity in the models of skin cancer and opportunistic skin infection. Dendritic cell phenotypes will be assessed using different single-cell and omics approaches established in our lab and functionally validated in transgenic mouse models that have defects in dendritic cell differentiation.

Due to their rapid activation and low frequency in tissues, the study of dendritic cells is challenging. Therefore, this PhD requires a strong background in immunology, previous experience with complex phenotyping of immune cells by flow cytometry (10+ markers) and previous experience with murine models of inflammation or infection. 

If you are interested in this project, please select Mayer (DCSkin) as your group 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

Bosteels C, Neyt K, Vanheerswynghels M, van Helden MJ, Sichien D, Debeuf N, De Prijck S, Bosteels V, Vandamme N, Martens L, Saeys Y, Louagie E, Lesage M, Williams DL, Tang SC, Mayer JU, Ronchese F, Scott CL, Hammad H, Guilliams M, Lambrecht BN. (2020) Inflammatory Type 2 CDCs Acquire Features of CDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.Immunity, 52 (6), 1039-1056 e9. Link

Kumamoto Y, Linehan M, Weinstein JS, Laidlaw BJ, Craft JE, Iwasaki A. (2013) CD301b+ dermal dendritic cells drive T helper 2 cell-mediated immunity.Immunity. 39(4):733–43. Link

Cook PC, Brown SL, Houlder EL, Baker S, Svedberg FR, Howell G, Bertuzzi M, Boon L, Konkel JE, Allen JE, MacDonald AS.(2023) Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation.bioRxiv p. 2023.11.24.568263. Link