Available online 26 July 2022, 101644

Tissue-resident cells and infiltrating immune cells shape local inflammatory responses.

The intracellularly complement system (aka the complosome) controls cell metabolism and function.

Mechanistic and structural details of the complosome are in the focus of current research.

C3-inhibiting peptides are promising candidates to curb tissue inflammation without immune suppression.

Hyperactivated local tissue is a cardinal feature of immune-mediated inflammatory diseases of various organs such as the joints, the gut, the skin, or the lungs. Tissue-resident structural and stromal cells, which get primed during repeated or long-lasting bouts of inflammation form the basis of this sensitization of the tissue. During priming, cells change their metabolism to make them fit for the heightened energy demands that occur during persistent inflammation. Epigenetic changes and, curiously, an activation of intracellularly expressed parts of the complement system drive this metabolic invigoration and enable tissue-resident cells and infiltrating immune cells to employ an arsenal of inflammatory functions, including activation of inflammasomes. Here we provide a current overview on complement activation and inflammatory transformation in tissue-occupying cells, focusing on fibroblasts during arthritis, and illustrate ways how therapeutics directed at complement C3 could potentially target the complosome to unprime cells in the tissue and induce long-lasting abatement of inflammation.

Inflammation

Arthritis

COVID-19

Cancer

Inflammatory tissue priming

Complement system

C3 therapeutics

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