DNMT1 and p38γ are inversely expressed in reactive non-metastatic lymph nodes burdened with colorectal adenocarcinoma.

DNMT1 and p38γ are inversely expressed in reactive non-metastatic lymph nodes burdened with colorectal adenocarcinoma.
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DOI:
10.1002/jha2.50
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发表时间:
2020-07
期刊:
EJHaem
影响因子:
--
通讯作者:
Rosen, Steven T.
Rosen, Steven T.
中科院分区:
其他
文献类型:
--
作者:
Zhang, Xu Hannah;Yin, Zhirong;Zhang, Aimin;Pillai, Raju;Armstrong, Brian;Rosen, Steven T.

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淋巴结是重要的前线防御免疫组织,也可以对抗炎症性疾病和癌症。当淋巴结暴露于抗原时,在新形成的生发中心(GC)内发生广泛的剧变,其分子机制仍然难以捉摸。最近,p38γ被确定为多种癌症的重要靶点,包括皮肤T细胞淋巴瘤(CTCL)。我们以前观察到,与正常细胞相比,p38γ在CTCL中过表达,但不清楚p38γ是否在患者GC的B或T淋巴细胞中表达以响应应激如癌症。因此,在本研究中,我们获得了癌病变(结直肠腺癌)附近的非转移性反应性淋巴结,然后对p38γ和其他相关标志物进行了免疫组化染色。我们首次观察到p38γ在GC中活化的B细胞和T辅助细胞的亮区表达,而GC B细胞的标志物DNA甲基转移酶1(DNMT 1)在GC的中心细胞和暗区高度表达。这种反比关系表明,p38γ在T细胞中有一种新的功能,它与B细胞在应激反应中相互作用。
Lymph nodes are important front‐line defense immune tissues, which also act against inflammatory diseases and cancer. Lymph nodes undergo extensive upheavals within newly formed germinal centers (GCs) when exposed to antigens, the molecular mechanisms of which remain elusive. Recently, p38γ was identified as an important target for multiple cancers, including cutaneous T‐cell lymphoma (CTCL). We previously observed that p38γ is overexpressed in CTCL versus normal cells, but it is not clear if p38γ is expressed in B or T lymphocytes of GCs of patients in response to a stress such as cancer. Therefore, in this study, we obtained non‐metastatic reactive lymph nodes adjacent to cancer lesions (colorectal adenocarcinoma), then performed multicolor immunohistochemical staining for p38γ and other relevant markers. We observed for the first time that p38γ was expressed in the light zone of activated B cells and T helper cells in GCs, whereas DNA‐methyltransferase 1 (DNMT1), a marker for GC B cells, was highly expressed in centrocytes and in the dark zone of GCs. This inverse relationship suggests a novel function for p38γ in T cells that cross‐talk to B cells in response to stress.
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