June 2021 - Thomas Krausgruber and Nikolaus Fortelny

Dr. Thomas Krausgruber and Dr. Nikolaus Fortelny

MedUni Wien RESEARCHER OF THE MONTH June 2021

Structural cells are key regulators of organ-specific immune responses

The human body consists of many specialized components: Bones and soft tissue provide structure, organs contribute to physiological functions such as digestion and CO2 exchange, and immune cells protect against pathogens. In order to make the human body efficient, many cell types and organs may play more than one role. The researchers Dr. Thomas Krausgruber and Dr. Nikolaus Fortelny in Prof. Christoph Bock's laboratory at CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, have now discovered a striking example of multi-tasking cells [1]. In their manuscript, published in the scientific journal Nature, the researchers analysed the epigenetic and transcriptional regulation in structural cells, including epithelium, endothelium, and fibroblasts. They found widespread activity of immune genes, suggesting that structural cells are not only essential building blocks of the body, but also contribute extensively to its defense against pathogens.

Selected Literature

1. Krausgruber T, Fortelny N, Fife-Gernedl V, Senekowitsch M, Schuster LC, Lercher A, Nemc A, Schmidl C, Rendeiro AF, Bergthaler A, Bock C: Structural cells are key regulators of organ-specific immune responses. Nature 2020. DOI:10.1038/s41586-020-2424-4
2. Abbas AK, Lichtman AH, Pillai S: Cellular and Molecular Immunology 9th edn; Elsevier, 2017.
3. Croft AP, Campos J, Jansen K, Turner JD, Marshall J, Attar M, Savary L, Wehmeyer C, Naylor AJ, Kemble S, Begum J, Dürholz K, Perlman H, Barone F, McGettrick HM, Fearon DT, Wei K, Raychaudhuri S, Korsunsky I, Brenner MB, Coles M, Sansom SN, Filer A, Buckley CD: Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 2019. DOI:10.1038/s41586-019-1263-7
4. Kinchen J, Chen HH, Parikh K, Antanaviciute A, Jagielowicz M, Fawkner-Corbett D, Ashley N, Cubitt L, Mellado-Gomez E, Attar M, Sharma E, Wills Q, Bowden R, Richter FC, Ahern D, Puri KD, Henault J, Gervais F, Koohy H, Simmons A: Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease. Cell 2018. DOI:10.1016/j.cell.2018.08.067
5. Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M, Udalova IA: IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol 2011. DOI:10.1038/ni.1990
6. Krausgruber T, Saliba D, Ryzhakov G, Lanfrancotti A, Blazek K, Udalova IA: IRF5 is required for late-phase TNF secretion by human dendritic cells. Blood 2010. DOI:10.1182/blood-2010-01-263020
7. Krausgruber T, Schiering C, Adelmann K, Harrison OJ, Chomka A, Pearson C, Ahern PP, Shale M, Oukka M, Powrie F: T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell responses in the intestine. Nat Commun 2016. DOI:10.1038/ncomms11627
8. Schiering C, Krausgruber T, Chomka A, Frohlich A, Adelmann K, Wohlfert EA, Pott J, Griseri T, Bollrath J, Hegazy AN, Harrison OJ, Owens BM, Lohning M, Belkaid Y, Fallon PG, Powrie F: The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 2014. DOI:10.1038/nature13577
9. Fortelny N, Cox JH, Kappelhoff R, Starr AE, Lange PF, Pavlidis P, Overall CM: Network analyses reveal pervasive functional regulation between proteases in the human protease web. PLoS Biology 2014. DOI:10.1371/journal.pbio.1001869
10. Fortelny N, Bock C: Knowledge-primed neural networks enable biologically interpretable deep learning on single-cell sequencing data. Genome Biology 2020. DOI:10.1186/s13059-020-02100-5
11.