This differential response to TLR9 prompted the investigators to explore the cellular and the molecular events that caused one strain to respond to therapy and the other to be resistant. Using a variety of approaches, the investigators found that TLR9-induced protection is mediated through the induction of a protein called type I IFN, which suppresses inflammation. The resistance to protection in the SCID mice is due to defective induction of type I IFN by TLR stimulation in mice of this genotype.
Further, they show that the inability of SCID to produce IFN is due to a mutation that impairs TLR9 signaling in this strain. Thus, type I IFN has a protective role in colon injury and protects against colonic inflammation.
In an accompanying commentary, Stefan Wirtz and Marcus Neurath state that, "These results underscore a potentially important protective role for type I IFNs in intestinal homeostasis and suggest that strategies to modulate innate immunity may be of therapeutic value for intestinal inflammatory conditions."
TITLE: Toll-like receptor 9-induced type I IFN protects mice from experimental colitis
University of California, San Diego La Jolla, CA USA
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This article is available at: http://www.jci.org/cgi/content/full/115/3/695
TITLE: Illuminating the role of type I IFNs in colitis
University of Mainz, Mainz, Germany
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Contact: Stacie Bloom
Journal of Clinical Investigation