Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis

摘要

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 in-fected 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.Genotypedependent 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.