Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 7, 2012; 18(13): 1459-1469
Published online Apr 7, 2012. doi: 10.3748/wjg.v18.i13.1459
Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis
Sarah J McCaskey, Elizabeth A Rondini, Jonathan F Clinthorne, Ingeborg M Langohr, Elizabeth M Gardner, Jenifer I Fenton
Sarah J McCaskey, Jenifer I Fenton, Department of Food Science and Human Nutrition, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, United States
Elizabeth A Rondini, Jonathan F Clinthorne, Elizabeth M Gardner, Department of Food Science Human Nutrition, Michigan State University, East Lansing, MI 48824, United States
Ingeborg M Langohr, Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, United States
Author contributions: McCaskey SJ and Rondini EA contributed equally to this work; McCaskey SJ and Rondini EA co-wrote this manuscript and McCaskey SJ, Rondini EA and Clinthorne JF performed the research; Langohr IM analyzed tissues for histopathology; Gardner EM assisted in experimental design; Fenton JI conceived the experimental design, assisted in experimental methods, and helped prepare the manuscript.
Supported by AgBio Research Center at Michigan State University
Correspondence to: Jenifer I Fenton, PhD, MPH, Department of Food Science and Human Nutrition, College of Osteopathic Medicine, Michigan State University, 208B G.M. Trout Building, East Lansing, MI 48824, United States. imigjeni@msu.edu
Telephone: +1-517-3558474 Fax: +1-517-3538963
Received: June 13, 2011
Revised: November 12, 2011
Accepted: December 31, 2011
Published online: April 7, 2012
Abstract

AIM: To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with Helicobacter hepaticus (H. hepaticus).

METHODS: SMAD3-/- (n = 19) and colitis-resistant SMAD3+/- (n = 24) mice (8-10 wk of age) were infected with H. hepaticus and changes in immune cell populations [T lymphocytes, natural killer (NK) cells, T regulatory cells] were measured in the spleen and mesenteric lymph nodes (MsLNs) at 0 d, 3 d, 7 d and 28 d post-infection using flow cytometry. Genotype-dependent changes in T lymphocytes and granzyme B+ cells were also assessed after 28 d in proximal colon tissue using immunohistochemistry.

RESULTS: As previously observed, SMAD3-/-, but not SMAD3+/- mice, developed colitis, peaking at 4 wk post-infection. No significant changes in T cell subsets were observed in the spleen or in the MsLNs between genotypes at any time point. However, CD4+ and CD8+/CD62Llo cells, an effector T lymphocyte population, as well as NK cells (NKp46/DX5+) were significantly higher in the MsLNs of SMAD3-/- mice at 7 d and 28 d post-infection. In the colon, a higher number of CD3+ cells were present in SMAD3-/- compared to SMAD3+/– mice at baseline, which did not significantly change during infection. However, the number of granzyme B+ cells, a marker of cytolytic lymphocytes, significantly increased in SMAD3-/- mice 28 d post-infection compared to both SMAD3+/- mice and to baseline values. This was consistent with more severe colitis development in these animals.

CONCLUSION: Data suggest that defects in SMAD3 signaling increase susceptibility to H. hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.

Keywords: Transforming growth factor-β, Colitis, Drosophila mothers against decapentaplegic, Colon cancer, T lymphocytes