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Tissue-Specific Differences in The Induction of Type 2 Immunity are Controlled by Specialized Dendritic Cell Subsets

In this Webinar, You Will Learn:

• How type 2 immune responses are controlled in barrier tissues
• Novel tools to investigate the initiation of type 2 immunity
• Role of tissue-specific dendritic cells in the induction of type 2 immunity
• Implications of tissue-specific control of type 2 immunity

About this Webinar:

To maintain an immunological balance and an intact epithelial barrier many tissues display a prominent anti-inflammatory pro-type 2 immune environment that can rapidly expel and entrap multicellular pathogens, neutralize toxins and support wound healing. Based on the unique physiological requirements of each barrier tissue, these responses are however specialized and induced by different populations of dendritic cells.
Previous research has shown that KLF4-expressing type 2 dendritic cells (cDC2) are drivers of enhanced type 2 immunity and present a high degree of phenotypic and functional heterogeneity in different tissues, suggesting that they adapt to diverse peripheral environments.
Using high-dimensional proteomic and single-cell RNA-sequencing technologies, we could show that cDC2 exhibit unique signatures in different murine tissues at the steady state. Focusing on the developmental requirements of these subsets we could show that CD11b-low cDC2, a population uniquely found in skin, required STAT6- and KLF4-dependent IL-13 signaling, whereas cDC2 subsets in lung and small intestine were STAT6-independent, with similar observations made in human skin.
In turn, analysis of healthy murine and human skin revealed low levels of type 2 cytokine production by innate lymphoid cells, Dendritic Epidermal T Cells and memory T cells. In healthy murine skin, IL-13, but not IL-4, was necessary and sufficient for the development of CD11b-low dendritic cells, suggesting a type 2 associated signaling circuit between type 2 cytokines, CD11b-low cDC2 and Th2 priming. In the absence of IL-13 signaling, dermal dendritic cells were stable in number and continued to take up antigen, but remained CD11b-hi. CD11b-hi dendritic cells furthermore showed defective activation in response to parasite antigens and a diminished ability to support IL-4+ GATA3+ Th2 cell differentiation.

Low levels of type 2 cytokines in healthy tissues might therefore play an important role in dendritic cell reprogramming and the generation of an anti-inflammatory pro-type 2 immune environment, which protects against multicellular pathogens but might also contribute to the development of allergies.

About Johannes Mayer

Johannes Mayer obtained his Bachelor of Science degree in Biology at the Technische Univeristät München (TUM) in 2012. After various research projects in Germany, France and the US he decided to focus his scientific career on studying the intestinal immune system and parasitic immune responses at the University of Glasgow, UK, where he was awarded a Master of Research (M.res.) degree in 2013 and a PhD in Immunology in 2017. He was intrigued by the possibility that different tissues could influence the differentiation and function of antigen-presenting cells and became a postdoctoral research fellow at the Malaghan Institute of Medical Research in Wellington, New Zealand in 2017 in the research group of Prof. Franca Ronchese.

Johannes Mayer relocated to the Philipps-University Marburg, Germany in 2021 where he founded the DCBiologyLab Marburg at the Department of Dermatology and Allergology to explore the role of dermal Dendritic cells in healthy and diseased skin and obtained his Habilitation/venia legendi in Molecular Immunology.

In September 2023 Johannes Mayer was appointed Professor for Dermatological Immunotherapy at the Department of Dermatology of the University Medical Center of the Johannes Gutenberg-University Mainz, Germany to pursue his goal to develop novel immunological therapies against type 2 immune responses.

Johannes Mayer has been awarded numerous prizes for his work, including the Werner-Müller-Preis by the German Society for Immunology in 2020, the European Macrophage and Dendritic Cell Society Young Investigator Research Award 2021, the Förderpreis ‘Neue immunologische Therapien atopischer/allergischer Erkrankungen’ by the Deutsche Gesellschaft für Allergologie und klinische Immunologie in 2022 and the Deutsche Neurodermitis-Preis awarded by the Deutsche Dermatologische Gesellschaft in 2023.


Recent Publications

Ferrer-Font L, Burn OK, Mayer JU, Price KM. (2024) Immunophenotyping challenging tissue types using high-dimensional full spectrum flow cytometry. Methods in Cell Biology, 0091-679X.

Schülke S, Gilles S, Jirmo AC, Mayer JU. (2023) Tissue-specific antigen-presenting cells contribute to distinct phenotypes of allergy. Eur. J. Immunol. 0:2249980.

Möbs C, Salheiser M, Bleise F, Witt M, Mayer JU. (2023) Basophils control T cell priming through soluble mediators rather than antigen presentation. Front. Immunol. 13:1032379.

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).

Ferrer-Font L, Mehta P, Harmos P, Schmidt AJ, Chappell S, Price KM, Hermans IF, Ronchese F, le Gros G, Mayer JU. (2020) High-Dimensional Analysis of Intestinal Immune Cells during Helminth Infection. eLife, 9, e51678.

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