Immune Activation in the Intestinal Mucosa Before the Onset of Colitis in Gαi2‐Deficient Mice

G‐protein subunit Gαi2‐deficient mice spontaneously develop an inflammatory bowel disease that clinically and histopathologically resembles ulcerative colitis in humans. The aim of this study was to determine whether immunological changes precede the development of colitis in Gαi2‐deficient mice. Therefore, Gαi2‐deficient mice with no clinical or histopathological signs of colitis were compared with Gαi2‐deficient mice with established colitis and wild‐type animals, concerning immunological parameters. Healthy Gαi2‐deficient mice displayed an increased frequency of CD4 + T cells and a decreased frequency of CD19 + B lymphocytes in the intestinal mucosa compared with control mice. The CD4 + population was characterized by a memory phenotype, i.e. increased expression of CD44 and decreased expression of CD45RB and CD62L, as well as increased expression of the mucosal homing receptors integrins α4β7 and αEβ7. Production of pro‐inflammatory cytokines, interleukin (IL)‐1β and interferon (IFN)‐γ, were increased in Gαi2‐deficient mice before clinical signs of disease were evident. In addition, total immunoglobulin (Ig)G and IgA levels in large intestinal secretions were increased significantly compared with wild‐type mice, and antibodies specific for the normal intestinal flora in large intestinal secretions were present in Gαi2‐deficient mice several weeks before the onset of colitis. In contrast, antibodies against tropomyosin, a putative autoantigen in human ulcerative colitis, were not found in Gαi2‐deficient mice before the onset of colitis, although they were present in animals with established disease. In conclusion, activation of the intestinal immune system precedes histopathological and clinical signs of inflammation in Gαi2‐deficient mice, suggesting that immune abnormalities play an important role in the induction of colitis.