ScienceDaily (Jan. 12, 2009) — A study from a team of researchers led by Dr. Andrew P. Makrigiannis, Director of the Molecular Immunology Research Unit at the IRCM, has identified a new mechanism regulating interferon production.

This discovery, co-authored by scientists from the International Medical Center of Japan (Tokyo), the National Cancer Institute at Frederick (Maryland) and the McGill Centre for the Study of Host Resistance, was published in the Journal of Experimental Medicine.

The plasmacytoid dendritic cell (pDC) is a type of white blood cell. The primary function of this cell type is to produce type I interferon when the body is infected by a virus. The pDC has special surface receptors that can detect many types of viruses. Type I interferon is thus very important for the clearance of a viral infection. "Working with mice, we have identified a mechanism that regulates the amount of interferon that is produced by pDCs, explains Dr. Makrigiannis. That mechanism is a protein-protein interaction between surface receptor Ly49Q and the class I major histocompatibility complex (MHC) molecule."

It is known that viruses often cause a decrease of class I MHC molecules on cells. The team of scientists believes that the reason for this may be to stop interferon production by the pDCs. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for the optimal activation of innate immune responses in vivo.

The discovery of this molecular strategy will very likely have a great impact in virology, and could eventually help physicians develop better therapeutic strategies to fight the infectious diseases afflicting their patients.

This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR). Lee-Hwa Tai is supported by a CIHR Cancer Training Program scholarship. Simon Bélanger is supported by a Fonds de la recherche en santé du Québec scholarship. Andrew P. Makrigiannis is supported by a New Investigator Award from the CIHR.

Journal reference:

1. Tai et al. Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC. Journal of Experimental Medicine, 2008; 205 (13): 3187 DOI: 10.1084/jem.20080718

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