Targeting Monocytes to Help Treat Autoimmune Disorders?

SUPPRESSION of the immune system in fighting diseases could be the fault of a population of white blood cells (WBCs), a group of studies led by St Jude Children’s Research Hospital, Memphis, Tennessee, USA, has shown.

According to Dr Peter Murray, co-author of one of these studies and a member of the St. Jude departments of Infectious Diseases and Immunology, St Jude Children’s Research Hospital, the group of WBCs discovered, called monocytic cells (MCs), are a particularly important target for the treatment of autoimmune disorders; sufferers of conditions such as rheumatoid arthritis could now benefit from relief provided by a decrease in immune response.

Using mouse models, the studies explored the regulation of two forms of programmed cell-death pathways, apoptosis and necroptosis, which get rid of damaged, dangerous, or redundant cells. The researchers found evidence that switching off the MCL1 gene in bone marrow led to the death of granulocytes, not monocytes, via apoptosis, and highlighted the protein FLIP as a major regulator of both apoptosis and necroptosis. Alternatively, eradicating FLIP in mice led to an over-abundance of granulocytes and a reduction in monocytes and related cells.

The studies also demonstrated how FLIP, MCL1, and MCL1-like protein, A1, work together to guarantee survival of the monocytic population of myeloid-derived suppressor cells; FLIP blocks programmed cell death via apoptosis and necrosis, but survival of MCs requires inhibition of the apoptotic pathway alone. Overall, Dr Murray commented: “Collaborating with the Opferman and Green laboratories gave us the tools we need to discriminate between the cell populations and identify monocytic cells as the important cells to target with immunotherapies.”

(Image: freeimages.com)

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