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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.
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 +) w ere significantly higher in the MsLNs of SMAD3 - / - mice at 7d and 28d 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 during infection. Host, 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.