Projects Offered

1 PhD project offered in the IPP winter call 2026/2027

Scientific Background

Regulatory T (Treg) cells are essential for controlling immune responses and preventing excessive inflammation. Currently, they are one of the most actively investigated cell types in immunology, with growing interest in their potential for treating autoimmune and inflammatory diseases. Their importance was further highlighted by the 2025 Nobel Prize in Physiology or Medicine, which recognized discoveries concerning peripheral immune tolerance mediated by Treg cells.

Tissue inflammation is often associated with increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6), which can affect the function and stability of Foxp3⁺ Treg cells. How Treg cells survive and maintain their immunosuppressive function in an inflammatory environment remains poorly understood. Understanding the natural mechanisms that allow Treg cells to adapt to inflammation could help improve Treg cell-based therapies for inflammatory and autoimmune diseases.

PhD Project: How interleukin-6 shapes regulatory T cells during inflammation

IL-6 signaling is mediated by its biologically relevant receptor, IL-6R. Our preliminary data show that IL-6R is expressed on Treg cell precursors in the thymus and on naïve mature Treg cells, but is downregulated on Treg cells at sites of inflammation. Treg cells isolated from IL-6-deficient mice, which lack IL-6 signaling during development, exhibit poor survival in IL-6-driven inflammatory conditions. These findings suggest that IL-6 signaling during Treg cell development may help establish the properties required for mature Treg cells to survive and function in inflammatory environments.

We hypothesize that Treg cells dynamically adjust their response to IL-6 during development and in peripheral tissues, allowing them to maintain immune suppression during inflammation. This regulation may involve changes in IL-6R expression and associated transcriptional and epigenetic mechanisms.

In this project, we will investigate how IL-6 signaling shapes the function and fitness of Treg cells in inflamed tissues. We will use mouse models with cytokine overproduction or cytokine/receptor deficiency, as well as spontaneous and experimentally induced inflammatory models. Treg cell transfer experiments will be used to study their survival, stability, and suppressive function. We will combine multicolor flow cytometry (FACS), mouse immunology models, and sequencing approaches to identify the cellular and molecular mechanisms that control Treg cell fitness during inflammation.

The project is strongly immunological and will provide training in experimental mouse immunology, T-cell biology, flow cytometry, and molecular approaches.

If you are interested in this project, please select Mufazalov/Waisman as your group preference in the IPP application platform.

Publications relevant to this project

Uhlfelder DC, Andruszewski D, Amelong LR, Schäfer HS, Hüttenschmidt M, Blanfeld M, Schelmbauer C, Ergün Z, Zonouzi AP, Hausen A, Zimmer S, Gaida MM, von Ungern-Sternberg S, Jurk K, Wunderlich TF, Publio GA, Nascimento DC, Alves-Filho JC, Korn T, Waisman A, Mufazalov IA (2026) Targeting soluble immunoglobulins ameliorates idiopathic multicentric Castleman disease in a mouse model.bioRxiv 2026.07.26.740764 Link

Mufazalov IA, Andruszewski D, Schelmbauer C, Heink S, Blanfeld M, Masri J, Tang Y, Schüler R, Eich C, Wunderlich FT, Karbach SH, Bluestone JA, Korn T, Waisman A (2020) Cutting Edge: IL-6-Driven Immune Dysregulation Is Strictly Dependent on IL-6R α-Chain Expression. J Immunol. Feb 15;204(4):747-751 Link

Heink S, Yogev N, Garbers C, Herwerth M, Aly L, Gasperi C, Husterer V, Croxford AL, Möller-Hackbarth K, Bartsch HS, Sotlar K, Krebs S, Regen T, Blum H, Hemmer B, Misgeld T, Wunderlich TF, Hidalgo J, Oukka M, Rose-John S, Schmidt-Supprian M, Waisman A, Korn T (2017) Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells. Nat Immunol. Jan;18(1):74-85 Link
 

Contact Details

Dr. Ilgiz Mufazalov
Email

Website UMC
Website TRR355_1
Website TRR355_2

Prof. Dr. Ari Waisman
Email