Mouse Model of Reversible Intestinal Inflammation

Current therapies to treat inflammatory bowel disease by dampening excessive inflammatory immune responses have had limited success (Reinisch et al., 2011; Rutgeerts et al., 2005; Sandborn et al., 2012). To develop new therapeutic interventions, Roper et al. calls for better understanding of the mechanisms that are operative during mucosal healing (Pineton de Chambrun et al., 2010).

Using the T cell transfer mediated colitis model, it was elegantly shown that intestinal inflammation can be reversed by the adoptive transfer of CD45RBlo regulatory T cells (Treg) in colitic animals, resulting in remission induction within 10-14 weeks post Treg transfer (Mottet et al., 2003). The kinetics of remission induction however varies depending on the expansion of transferred Treg and it can be difficult to synchronize the onset of remission between animals of same experimental group. To overcome the unpredictable timing and extent of remission induction, their team developed a new mouse model of reversible intestinal inflammation in which intestinal inflammation (induced by the adoptive transfer of naïve CD45RBhi T cells in lymphopenic animals) can be reversed by depletion of colitogenic CD4+ T cells in mice with established disease, resulting in reproducible induction of remission from colitis (Brasseit et al., 2016).

To this end, a reversible model of colitis was developed in which colitis induced by adoptive transfer of naïve CD4+ CD45RBhi T cells in lymphopenic mice can be reversed through depletion of colitogenic CD4+ T cells (Brasseit et al., 2016).