Introduction Intestinal Inflammatory Disease (IID) as a primary immunodeficiency depends on mutations in the NADPH oxidase complex, responsible for the production of reactive oxygen species (ROS). One of the most common clinical patterns in IID is chronic colitis. Ncf1-mutation in mice leads to deficiency in ROS, rendering them susceptible to autoimmunity. As in humans, Ncf1-mutation leads to the lack of ROS in B10. Q mice. We used these mutant mice to study how the lack of ROS influences DSS-induced colitis, its transitional recovery and a second colitis induction.
Material and Methods Colitis was induced in wild type (WT) and Ncf1-mutant (Ncf1) B10. Q mice by administration of 3,0% DSS in the drinking water for one week. Two experiments were made: the first one where the mice were submitted to a 7 days induction and 21 days of resting, the second one included 7 days of induction, followed by 14 days of resting and another 7 days cycle. Mice were sacrificed before the experiment had started and at days 7, 23 and 30. During the experiment we monitored clinical scores of colitis. The colon was removed and folded into a Swiss roll and sections of the colons were stained with HE. Leukocytes subsets from mesenteric lymph-nodes were analysed by flow citometry.
Results/ Conclusions The clinical scores were more severe in Ncf1 than WT mice also with a poor recovery. The cell population study showed in Ncf1 an aberrant pro-inflammatory immune response comparing to WT and also a more inefficient recovery. This severe colitis was mediated by increased local expression of cytokines (IL-6, IL-10, TNF-α, IFN-γ and IL-17A) and phosphorylation of LRRK2. Histological analyses revealed that Ncf1 mice had a more severe disease with poor proximal epithelium recovery, signs of dysplasia and with some of them developing colon carcinoma. These results suggest that ROS are crucial for leukocyte recruitment and tissue-repair in DSS-induced colitis.