Christina Zielinski

The major focus of my laboratory is to work towards a comprehensive mechanistic foundation of human T cell regulation and to transform this knowledge into novel strategies for future precision immunotherapies. My research agenda covers three main topics: 1) the molecular regulation of human T cell properties, 2) the regulation of tissue-specific human T cell fates, and 3) the role of innate immune signaling platforms in T cells.

We investigate the fundamental mechanisms that drive the functional diversification of human T helper cells. Our research has revealed novel T cell identities such as pro- and anti-inflammatory Th17 cells (Zielinski et al. Nature 2012), GMCSF– and IL-1a–producing T cells (Noster al. al Sci Transl Med 2014, Chao et al. Nat Immunol 2023) and their underlying molecular regulation. This contributed to our understanding of immune dysregulation with major implications for the pathogenesis of autoimmune diseases.

Most insights about the human immune system stem from investigating circulating T cells in the blood, which, however, only represent 2% of our body’s T cells. It remains unknown how and which kind of T cells acquire residence in different human tissues, how this affects their regulation and function and finally their role in long-lasting immune protection from infections. My group has previously identified allogeneic stem cell transplantation as a clinical model to track the fate of incoming donor T cells and to monitor the durability of host T cells across human tissues (de Almeida et al. Sci Immunol 2022). This now allows us to decode the spatial and temporal identity of human circulating and resident T cells at single-cell resolution.

We also study how T cells communicate with their tissue microenvironment, with particular emphasis on ionic signaling. We discovered that sodium chloride enhances CD8+ T cell cytotoxicity, improving tumor control (Soll et al., Nat Immunol 2024). Tissue sodium accumulation also drives Th2 polarization and allergic disease (Noster et al., Sci Transl Med 2019), while mitigating autoimmunity (Noster et al., J Clin Invest 2020). Additional functions of ionic signals are currently under investigation.

Finally, we explore the role and regulation of innate signalling platforms in human T cells and their impact on host defense. We have recently described NLRP3-inflammasome activation in Th17 cells. T cells repurpose NLRP3-inflammasome for secretion of the danger signal IL-1a via GSDME pores (Chao et al. Nat Immunol 2023). We are now investigating how these previously overlooked pathways drive novel T cell functions in health and disease.

My lab‘s uniquely human-centered approach enables direct translation of mechanistic insights into therapeutic targets and adoptive T cell therapies.