Department of Food Science and Human Nutrition, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, United States.
World J Gastroenterol. 2012 Apr 7;18(13):1459-69. doi: 10.3748/wjg.v18.i13.1459.
To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with Helicobacter hepaticus (H. hepaticus).
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.
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(lo) 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.
Data suggest that defects in SMAD3 signaling increase susceptibility to H. hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.
鉴定和描述果蝇母体对抗 decapentaplegic（SMAD）3 依赖性免疫细胞群体变化，这些变化发生在感染 Helicobacter hepaticus（H. hepaticus）后。
SMAD3（-/-）（n = 19）和结肠炎抗性 SMAD3（+/-）（n = 24）小鼠（8-10 周龄）感染 H. hepaticus，使用流式细胞术在感染后 0 天、3 天、7 天和 28 天测量脾脏和肠系膜淋巴结（MsLN）中免疫细胞群体[T 淋巴细胞、自然杀伤（NK）细胞、T 调节细胞]的变化。在感染后 28 天，还使用免疫组织化学评估结肠炎抗性 SMAD3（+/-）和 SMAD3（-/-）小鼠近端结肠组织中 T 淋巴细胞和颗粒酶 B（+）细胞的基因型依赖性变化。
如前所述，SMAD3（-/-），而不是 SMAD3（+/-），发展为结肠炎，在感染后 4 周达到高峰。在任何时间点，两种基因型的脾脏或 MsLN 中 T 细胞亚群均无明显变化。然而，在感染后 7 天和 28 天，SMAD3（-/-）小鼠的 MsLN 中 CD4（+）和 CD8（+）/CD62L（lo）细胞（效应 T 淋巴细胞群）以及 NK 细胞（NKp46/DX5（+））显著升高。在结肠中，与 SMAD3（+/-）相比，SMAD3（-/-）小鼠在基线时存在更多的 CD3（+）细胞，而在感染过程中，这些细胞数量没有显著变化。然而，在感染后 28 天，SMAD3（-/-）小鼠中的颗粒酶 B（+）细胞（细胞毒性淋巴细胞的标志物）数量显著增加，与 SMAD3（+/-）小鼠和基线值相比都显著增加。这与这些动物中更严重的结肠炎发展一致。
数据表明，SMAD3 信号传导缺陷通过效应淋巴细胞的异常激活和/或失调增加了对 H. hepaticus 诱导的结肠炎的易感性。
