Previous data had shown that TLR9, in particular, could set into motion an anti-inflammatory program to ease colitis in experimental animals. In a study appearing in the March 1 issue of the Journal of Clinical Investigation, Eyal Raz and colleagues from the University of California San Diego, explored how TLR9 eased inflammation and offered relief in colitis.
In this study, researchers administered TLR9 activators to two different groups of mice that appear similar because both of them do not produce T or B immune cells, but are actually genetically different, because they come from different strains. TLR9 activators, given to one group of mice, called RAG mice, inhibited the severity of experimental colitis but had no effect on the other group of mice, called SCID mice.
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
AUTHOR CONTACT: Eyal Raz
University of California, San Diego La Jolla, CA USA
Phone: (858) 534-5444; Fax: (858) 534-5399; E-mail: eraz@ucsd.edu
This article is available at: http://www.jci.org/cgi/content/full/115/3/695
ACCOMPANYING COMMENTARY:
TITLE: Illuminating the role of type I IFNs in colitis
AUTHOR CONTACT: Markus Neurath
University of Mainz, Mainz, Germany
Phone: 49-6131-172374; Fax: 49-6131-39175508; E-mail: neurath@1-med.klinik.uni-mainz.de
This article is available at: http://www.jci.org/cgi/content/full/115/3/586
Journal of Clinical Investigation