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


    McNamee, Eóin N. and Wermers, Joshua D. and Masterson, Joanne C. and Collins, Colm B. and Lebsack, Matthew D.P. and Fillon, Sophie A. and Robinson, Zachary and Grenawalt, Joanna and Lee, James J. and Jedlicka, Paul and Furuta, Glenn T. and Rivera-Nieves, Jesus (2010) A Novel Model of TH2-polarized Chronic Ileitis: The SAMP1 Mouse. Inflammatory Bowel Diseases, 16 (5). pp. 743-752. ISSN 1536-4844

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    Abstract

    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.

    Item Type: Article
    Keywords: Novel Model; TH2-polarized Chronic Ileitis; SAMP1 Mouse;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12567
    Identification Number: https://doi.org/10.1002/ibd.21148
    Depositing User: Eoin McNamee
    Date Deposited: 09 Mar 2020 17:10
    Journal or Publication Title: Inflammatory Bowel Diseases
    Publisher: Oxford University Press
    Refereed: Yes
    URI:

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