Neuro-Immune interactions in the skin in the context of type 2 immunity

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

Scientific Background

Type 2 immune signals control a variety of innate and non-immune mechanisms linked to parasite expulsion and toxin inactivation. While highly relevant in the context of evolution, uncontrolled type 2 immune activation has been linked with negative outcomes, such as allergies and immune suppression in many industrialized countries. Local type 2 immune cell circuits play a major role in tissue-specific disease progression and play a prominent role in barrier tissues.

These type 2 immune circuits are controlled by alarmin or neuropeptide signalling and alarmin responses have a strong activating effect on Innate Lymphoid cells (ILC), Dendritic Cells (DC) and T cells. Our preliminary work however suggests neuro-immune signalling plays an important role in defining the homeostatic type 2 signature prominent in healthy skin, while alarmin signalling drives detrimental type 2 immunity.

PhD Project: Defining dermal Neuro-Immune Interactions that drive beneficial and detrimental type 2 immunity

Overall Aim: To understand the properties of dermal Neuro-Immune Networks in the context of homeostatic type 2 immune signalling and wound healing vs. neurodermitis associated inflammation.

Cutting-edge techniques, like scRNA-seq, 3D imaging and high dimensional flow cytometry, will be employed to comprehensively characterize the phenotypic and functional properties of dermal Neuro-Immune Networks in the murine skin. Interactions will be validated in vitro and molecular signalling cascades assessed in important immune cell populations, such as ILC, DC and T cells.

These interactions will be monitored in the context of neurodermitis associated inflammation and transgenic mouse strains will be used to determine the importance of neuropeptide expression and signalling in the context of disease.

If you are interested in this project, please select Mayer (Neuro) 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

Schülke S, Gilles S, Jirmo AC, Mayer JU. (2023) Tissue-specific antigen-presenting cells contribute to distinct phenotypes of allergy. Eur J Immunol. Dec;53(12):e2249980.  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

Bielecki P, Riesenfeld SJ, Hütter JC, Torlai Triglia E, Kowalczyk MS, Ricardo-Gonzalez RR, Lian M, Amezcua Vesely MC, Kroehling L, Xu H, Slyper M, Muus C, Ludwig LS, Christian E, Tao L, Kedaigle AJ, Steach HR, York AG, Skadow MH, Yaghoubi P, Dionne D, Jarret A, McGee HM, Porter CBM, Licona-Limón P, Bailis W, Jackson R, Gagliani N, Gasteiger G, Locksley RM, Regev A, Flavell RA. (2021) Skin-resident innate lymphoid cells converge on a pathogenic effector state. Nature. Apr;592(7852):128-132. Link

Xu H, Ding J, Porter CBM, Wallrapp A, Tabaka M, Ma S, Fu S, Guo X, Riesenfeld SJ, Su C, Dionne D, Nguyen LT, Lefkovith A, Ashenberg O, Burkett PR, Shi HN, Rozenblatt-Rosen O, Graham DB, Kuchroo VK, Regev A, Xavier RJ. (2019) Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses.Immunity. Oct 15;51(4):696-708.e9. Link

 

Contact Details

Prof. Dr Johannes Mayer
University Medical Center Mainz
Department of Dermatology

Email
Website UMC
Website Mayer Lab