A Novel Model of TH2-polarized Chronic Ileitis: The SAMP1 Mouse

Background & Aims—SAMP1/Yit mice develop spontaneous, segmental, transmural ileitis recapitulating many features of Crohn’s disease (CD). The ileitic phenotype may have arisen during crosses of SAMP1 mice selected for the presence of skin lesions. We hereby describe that the original SAMP1 strain similarly develops ileitis. Our aim was to characterize the histopathological and immunological features of this model and assess its responsiveness to standard IBD therapy. Methods—The time course of histopathological features of ileitis was assessed. Immune compartments were characterized by flow cytometry. Ileal cytokine profiles and transcription factors were determined by real-time RT-PCR. Finally, response to corticosteroid therapy and its effect on immune compartments and cellularity was evaluated. Results—Histological features and time course of disease were conserved, compared to those reported in SAMP1/Yit strains, with similar expansion of CD19+, CD4+ and CD8+ effector (CD44highCD62Llow), and central memory lymphocytes (CD44highCD62Lhigh). However, different from SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial TH1 polarization followed by TH2-polarized profile accompanied by prominent eosinophilia during late disease. Lastly, corticosteroids attenuated ileitis resulting in decreased lymphocyte subsets and cellularity of compartments. Conclusions—Here we report that the ileitic phenotype of SAMP1-related strains was already present in the original SAMP1 strain. By contrast the cytokine profile within terminal ilea of SAMP1 is distinct from the mixed TH1/TH2 profile of SAMP1/YitFc mice during late disease, as it shows predominant TH2 polarization. Dissemination of these strains may advance our understanding of CD pathogenesis, which in 60% of patients involves the terminal ileum