TY - JOUR
T1 - Novel model of TH2-polarized chronic ileitis
T2 - The SAMPl mouse
AU - McNamee, Eoin N.
AU - Wermers, Joshua D.
AU - Masterson, Joanne C.
AU - Collins, Colm B.
AU - Matthew, D. P.
AU - Lebsack, B. A.
AU - Fillon, Sophie
AU - Robinson, Zachary D.
AU - Grenawalt, Joanna
AU - Lee, James J.
AU - Jedlicka, Paul
AU - Furuta, Glenn T.
AU - Rivera-Nieves, Jesús
PY - 2010
Y1 - 2010
N2 - Background: 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 inflammatory bowel disease (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 reverse-transcription polymerase chain reaction (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 (CD44high CD62LloW), and central memory lymphocytes (CD44 highCD62Lhigh). However, different from SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial TH1 polarization followed, by TH2-polarized profile accompanied by prominent eosinophiiia 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 SAMP 1-related strains was already present in the original SAMP1 strain. By contrast, the cytokine profile within, the terminal ilea of SAMP1 is distinct from the mixed T H1/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.
AB - Background: 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 inflammatory bowel disease (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 reverse-transcription polymerase chain reaction (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 (CD44high CD62LloW), and central memory lymphocytes (CD44 highCD62Lhigh). However, different from SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial TH1 polarization followed, by TH2-polarized profile accompanied by prominent eosinophiiia 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 SAMP 1-related strains was already present in the original SAMP1 strain. By contrast, the cytokine profile within, the terminal ilea of SAMP1 is distinct from the mixed T H1/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.
KW - Crohn's disease
KW - Polarization
KW - SAMP1
KW - TH2
UR - http://www.scopus.com/inward/record.url?scp=77950640810&partnerID=8YFLogxK
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U2 - 10.1002/ibd.21148
DO - 10.1002/ibd.21148
M3 - Article
C2 - 19856411
AN - SCOPUS:77950640810
SN - 1078-0998
VL - 16
SP - 743
EP - 752
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 5
ER -