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Granulomatous diseases affect millions of people worldwide. The diseases lead to inflammation of the lungs, intestines or blood vessels, among other things, and are characterized by the formation of small nodules called granulomas. These nodules are formed by highly structured immune cells, primarily from multinucleated macrophages. Due to their size, these are also known as giant cells. Until now, it was assumed that multinucleated macrophages are formed by the fusion of several cells. Researchers led by Dr. Antigoni Triantafyllopoulou, group leader at the Department of Rheumatology and Clinical Immunology (Medical Director: Prof. Dr. Reinhard Voll) and the Center for Chronic Immunodeficiency (CCI) at the Medical Center of Freiburg, together with colleagues from the Mainz University Medical Center, the Max Planck Institute for Immunology and Epigenetics in Freiburg, the University of Würzburg and the National Kapodistrias University of Athens, have found a completely different explanation. They demonstrated that the giant cells are the result of defective cell division, in which the genetic material and cell size are doubled but the cell does not subsequently divide. The development of such giant cells is the body's response to genetic damage. The study was published on November 17, 2016 in the renowned journal Cell.

Granulomas can develop in response to persistent infectious or inflammatory stimuli that the organism cannot stop. For this reason, granulomatous diseases of non-infectious origin are often treated by suppressing the immune system. However, this also increases the risk of infections. "The new findings on the development of giant immune cells could now trigger the development of completely new therapeutic approaches for granulomatous diseases," says study leader Dr. Triantafyllopoulou. The study was largely funded as part of the Collaborative Research Center (CRC) 1160 "IMPATH".

Original title of the publication: DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas

DOI: 10.1016/j.cell.2016.09.054

Link to the study: http://www.cell.com/cell/fulltext/S0092-8674%2816%2931339-3

Further information:

Center for Chronic Immunodeficiency

Collaborative Research Center 1160 (IMPATH )

Contact:
Dr. Antigoni Triantafyllopoulou
Research Group Leader
Department of Rheumatology and Clinical Immunology
Medical Center - University of Freiburg
Phone: 0761 270-62170
antigoni.triantafyllopoulou@uniklinik-freiburg.de