Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer.
Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer.
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DOI：
10.1038/ncomms10517
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发表时间：
2016-02-04
影响因子：
16.6
通讯作者：
Wang TC
中科院分区：
文献类型：
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作者：
Dubeykovskaya Z;Si Y;Chen X;Worthley DL;Renz BW;Urbanska AM;Hayakawa Y;Xu T;Westphalen CB;Dubeykovskiy A;Chen D;Friedman RA;Asfaha S;Nagar K;Tailor Y;Muthupalani S;Fox JG;Kitajewski J;Wang TC
CD 11b +Gr-1+骨髓源性抑制细胞（MDSC）在癌症期间在脾脏中扩增，并通过抑制细胞毒性T细胞促进进展。涉及迷走神经和记忆T细胞的抗炎反射弧对于解决急性炎症是必要的。这种神经回路的故障可能会促进致癌性炎症和改变肿瘤免疫力。在这里，我们表明，脾TFF 2，分泌的抗炎肽，是由迷走神经调节的记忆T细胞通过CXCR 4抑制MDSC的扩张。脾脏去神经支配中断了抗炎神经弧，导致MDSC和结直肠癌的扩张。Tff 2的缺失重演了脾去神经支配促进癌发生。通过转基因过表达TFF 2、腺病毒转染TFF 2或移植表达TFF 2的骨髓可抑制大肠癌的发生。TFF 2对抗炎反射弧很重要，在抑制MDSC增殖中起重要作用。TFF 2提供了预防和治疗癌症的潜在方法。 在结直肠炎症和癌症期间，骨髓细胞在脾脏中积聚并抑制宿主免疫反应。在这项研究中，作者使用结肠炎小鼠模型来证明，在迷走神经刺激后，脾脏记忆T细胞释放TFF 2，抑制骨髓细胞的扩增和癌症进展。
CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) expand in the spleen during cancer and promote progression through suppression of cytotoxic T cells. An anti-inflammatory reflex arc involving the vagus nerve and memory T cells is necessary for resolution of acute inflammation. Failure of this neural circuit could promote procarcinogenic inflammation and altered tumour immunity. Here we show that splenic TFF2, a secreted anti-inflammatory peptide, is released by vagally modulated memory T cells to suppress the expansion of MDSCs through CXCR4. Splenic denervation interrupts the anti-inflammatory neural arc, resulting in the expansion of MDSCs and colorectal cancer. Deletion of Tff2 recapitulates splenic denervation to promote carcinogenesis. Colorectal carcinogenesis could be suppressed through transgenic overexpression of TFF2, adenoviral transfer of TFF2 or transplantation of TFF2-expressing bone marrow. TFF2 is important to the anti-inflammatory reflex arc and plays an essential role in arresting MDSC proliferation. TFF2 offers a potential approach to prevent and to treat cancer. During colorectal inflammation and cancer, myeloid cells accumulate in the spleen and suppress the host immunity response. In this study, the authors use a mouse model of colitis to demonstrate that upon vagus stimulation splenic memory T cells release TFF2, which suppresses the expansion of myeloid cells and cancer progression.