Tissue Aspects of Immunity and Inflammation

Inflammation is crucial to maintain tissue homeostasis in response to physical, chemical or infectious agents.  If inflammation fails to stop timely, however, it quickly becomes a pathological process, causing severe collateral damage to the tissue that can be debilitating or even life-threatening. In chronic inflammatory diseases (CIDs) such as rheumatoid arthritis, pemphigoid diseases, systemic lupus erythematosus, and many others, inflammation becomes self-perpetuating even if the initial trigger might be long gone. 

Tissues have the ability to remember past encounters with pathogens, wounds and/or other irritants, and to react more strongly to the next experience. Although this priming of the tissue bears a paramount role for host survival and defence from pathogens, maladapted inflammatory priming drives inflammatory pathologies (the Dr. Jekyll and Mr. Hyde aspect of tissue immunity). Non antigen-specific inflammatory priming is propagated at the epigenetic and metabolic level. Although still unfolding, epigenetic memories of inflammation and metabolic rewiring of inflammatory cells have now been linked to many CIDs. 

One of our key concepts is that long-lived tissue-resident cells (the ‘pathogenic stroma‘) promote inflammatory tissue priming and thus provide the unifying patho-physiological targets that link the site-specific clinical manifestation of CIDs to their molecular pathology. However, stromal cells do not act in isolation but in a dense interplay with infiltrating inflammatory cells, such as neutrophils, monocytes and lymphocytes. 

Our research focuses on finding the master switches that determine sustained resolution (“cure”) or persistence/relapse of inflammation. A special focus is laid on the role of tissue-resident stromal cells (e.g., fibroblasts), of neutrophils and the interaction between these cell types and with cells of the adaptive immune system. To this end, we are performing multi-parameter characterization and modulation of tissue microenvironments for inhibition of pathogenic function of tissue-occupying cells and their interaction with systemically acting classical immune cells.

Key conceptual publications:

Jasna Friščić, M. Hoffmann. Stromal cell regulation of inflammatory responses, Curr Opin Immunol. 2022 Feb:74:92-99. doi: 10.1016/j.coi.2021.10.006. Epub 2021 Nov 27.

M. Hoffmann , H.Kirchner, G.Krönke , G.Riemekasten, M. Bonelli. Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases, Ann Rheum Dis. 2024 May 3:ard-2023-224092., doi: 10.1136/ard-2023-224092.

K. Dutta , J. Friscic, M. Hoffmann. Targeting the tissue-complosome for curbing inflammatory disease, Semin Immunol. 2022 Mar:60:101644.  doi: 10.1016/j.smim.2022.101644. Epub 2022 Jul 26.

M. Hoffmann, H. Griffiths, The dual role of Reactive Oxygen Species in autoimmune and inflammatory diseases: evidence from preclinical models, Free Radic Biol Med. 2018 Sep:125:62-71.
doi: 10.1016/j.freeradbiomed.2018.03.016. Epub 2018 Mar 15.

M. Euler, M. Hoffmann, The double-edged role of neutrophil extracellular traps in inflammation, Biochem Soc Trans. 2019 Dec 20;47(6):1921-1930, doi: 10.1042/BST20190629.