Novel model of TH2-polarized chronic ileitis: the SAMP1 mouse.
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 (CD44(high) CD62L(low)), and central memory lymphocytes (CD44(high)CD62L(high)). However, different from SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial T(H)1 polarization followed by T(H)2-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 the terminal ilea of SAMP1 is distinct from the mixed T(H)1/T(H)2 profile of SAMP1/YitFc mice during late disease, as it shows predominant T(H)2 polarization. Dissemination of these strains may advance our understanding of CD pathogenesis, which in 60% of patients involves the terminal ileum.
McNamee
Eoin N
EN
Division of Gastroenterology, University of Colorado Health Sciences Center, Denver, Colorado 80045, USA.
Wermers
Joshua D
JD
Masterson
Joanne C
JC
Collins
Colm B
CB
Lebsack
Matthew D P
MD
Fillon
Sophie
S
Robinson
Zachary D
ZD
Grenawalt
Joanna
J
Lee
James J
JJ
Jedlicka
Paul
P
Furuta
Glenn T
GT
Rivera-Nieves
Jesçs
J
D000818:Animals; D002478:Cells, Cultured; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D007079:Ileitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D007156:Immunologic Memory / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D050990:GATA3 Transcription Factor; D012333:RNA, Messenger; D003907:Dexamethasone