Newly Discovered Phagocyte Plays Role in Autoimmune Disease

MANHASSET, N.Y./PRNewswire/ -- Hemophagocytes, a newly identified population of phagocytes, may have a direct impact on patients with a variety of autoimmune diseases, researchers announced in the January 11 issue of Science.

Many acute inflammatory disorders and infections are associated with a reduction in the number of mature blood cells – termed cytopenias – including anemia and thrombocytopenia. However, the mechanisms leading to these disease manifestations are not well understood by the scientific and medical community. The ingestion of bacteria or other material by phagocytes in red blood cells, platelets and leukocytes can be a major contributor to acute cytopenias.

Knowing this, Betsy J. Barnes, PhD, professor and head of the Laboratory of Autoimmune and Cancer Research at the Feinstein Institute, along with collaborators at Benaroya Research Institute and University of Washington in Seattle, conceived that specialized phagocytes may develop in these inflammatory conditions in response to the signals of pattern recognition receptors, such as Toll-like receptors (TLR). TLR are known to trigger cytokine production, however the role of TLR in specifying myeloid cell development remains poorly understood. The researchers hypothesized that TLR signaling may drive a unique cell in the body that is apparent at sites of infection and has a macrophage phenotype.

Through the researcher's test – an in vitro culture system in which bone marrow common myeloid progenitors (CMP) were cultured with the TLR7 agonist R848 – they uncovered a novel cell type and mechanism by which TLR signaling impacts phagocytosis. Hemophagocytes are responsible for anemia associated with inflammation and infection, which shows that specialized phagocytes required for inflammation-induced cytopenias develop in situations of acute inflammation and possibly autoimmune diseases.

"Findings implicating an important role for the transcription factor interferon regulatory 5 (IRF5) in development of hemophagocytes may have direct impact on patients with a variety of autoimmune diseases, including macrophage activation syndrome (MAS), in which IRF5 genetic variants have been associated with risk of MAS," said Dr. Barnes.

MAS is a life-threatening complication of rheumatic disease that, for unknown reasons, occurs much more frequently in individuals with systemic juvenile idiopathic arthritis (SJIA) and in those with adult-onset Still disease.

Contact: Emily Ng

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