AIM： To identify and characterize drosophila mothers against decapentaplegic （SMAD）3-dependent changes in immune cell populations following infection with He- Iicobacter hepaticus （H. hepaticus）. METHODS： SMAD3/...AIM： To identify and characterize drosophila mothers against decapentaplegic （SMAD）3-dependent changes in immune cell populations following infection with He- Iicobacter hepaticus （H. hepaticus）. METHODS： SMAD3/ （n = L9） and colitis-resistant SMAD3＋/ （n = 24） mice （8-10 wk of age） were in- fected with/-/, 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＋/ CD62L＋＋ 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-in- fection. In the colon, a higher number of CD3＋ cells were present in SMAD3＋ compared to SMAD3＋/- mice at base- line, which did not significantly change during infection. However, the number of granzyme B＋ cells, a marker of cytolytic lymphoo/tes, 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 lymphoo/tes.展开更多
基金Supported by AgBio Research Center at Michigan State University
文摘AIM： To identify and characterize drosophila mothers against decapentaplegic （SMAD）3-dependent changes in immune cell populations following infection with He- Iicobacter hepaticus （H. hepaticus）. METHODS： SMAD3/ （n = L9） and colitis-resistant SMAD3＋/ （n = 24） mice （8-10 wk of age） were in- fected with/-/, 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＋/ CD62L＋＋ 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-in- fection. In the colon, a higher number of CD3＋ cells were present in SMAD3＋ compared to SMAD3＋/- mice at base- line, which did not significantly change during infection. However, the number of granzyme B＋ cells, a marker of cytolytic lymphoo/tes, 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 lymphoo/tes.
