Prof. Manfred Kopf

Keywords

cytokines, inflammation, infections, innate & adaptive immunity

What we investigate

The research of the Kopf lab is focused on understanding inflammatory and infectious diseases with a particular interest in the role the role of cytokines in these processes.

Our research in more detail

Research Figure Kopf
The figure shows the heterogeneity of T helper cell cytokine responses in animal models of infection and autoimmunity as revealed by high-dimensional analysis using CyTOF. (A,B) Mice were infected with influenza and lung-infiltrating T-cells were analyzed by CyTOF. Boolean subsets (A) and color-coded UMAP plots depicting the expression of the indicated cytokines (B). (C,D) Mice were infected with a nematode. Lungs and mediastinal lymph nodes were analyzed by CyTOF. UMAP maps show the expression of the indicated factors (C), and the heatmap shows the Boolean subsets (D). (E) Sorted naive CD4+ T-cells were injected alone or with Treg cells into Rag1−/− mice. After 8 weeks, T-cells in colonic lamina propria were analyzed by CyTOF and data presented as UMAP plots show the expression of the indicated factors in T-cells from mice that received naive T-cells only.

Overshooting immune responses and inflammation contribute to wide range of chronic diseases including atherosclerosis, type 2 diabetes, psoriasis, asthma, and autoimmune diseases, which pose the greatest threat to human health worldwide due to a high prevalence and incidence. On the other hand, potent immune responses are required to control infectious disease and eliminate tumours. The molecular pathways underlying chronic inflammatory disorder and defence against pathogens or tumours are often overlapping, with T cells, myeloid cells, and cytokines produced by them playing a central role. We are studying the cellular and molecular mechanisms of inflammation using several genetically modified animal models. Moreover, the lab has started to study the role of the major redox pathways, including the glutathione/glutaredoxin, thioredoxin, and Nrf2 pathway in T cell- and myeloid cell-mediated inflammation. Recently, we also established a novel and unique technology platform for unbiased identification of peptide epitopes recognized by T cells that can be harnessed for personalized immunotherapy of cancer or autoimmunity, and vaccination against infectious diseases.

Selected publications

SKINTEGRITY.CH Principal Investigators are underlined:

  • Tortola L, Jacobs A, Pohlmeier L, Obermair FJ, Ampenberger F, Bodenmiller B, and Kopf, M. (2020). High-dimensional T helper cell profiling reveals a broad diversity of stably committed effector States and uncovers interlineage relationships. Immunity, in press.
  • Kisielow J*, Obermair FJ, and Kopf M* (2019). Deciphering CD4(+) T cell specificity using novel MHC-TCR chimeric receptors. Nat Immunol 20, 652-662. *Joint corresponding authors.
  • Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y, Hersberger M, and Kopf M (2013). Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1alpha and sterile vascular inflammation in atherosclerosis. Nat Immunol 14, 1045-1053.
  • Nobs SP, Natali S, Pohlmeier L, Okreglicka K, Schneider C, Kurrer M, Sallusto F, and Kopf M. (2017). PPARg in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation. J Exp Med 214, 3015-3035.
  • Tortola L, Rosenwald E, Abel B, Blumberg H, Schafer M, Coyle AJ, Renauld JC, Werner S, Kisielow J*, and Kopf M* (2012). Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. J Clin Invest 122, 3965-3976. Joint corresponding authors.