Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation
Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation
复制标题
DOI：
10.1038/s41590-018-0298-5
复制
发表时间：
2019-01
影响因子：
30.5
通讯作者：
S. Zundler;E. Becker;M. Spocinska;Monique Slawik;Loreto Parga-Vidal;Regina Stark;Maximilian Wiendl;R. Atreya;T. Rath;M. Leppkes;K. Hildner;R. López-Posadas;S. Lukassen;A. Ekici;C. Neufert;I. Atreya;K. V. van Gisbergen;M. Neurath
中科院分区：
文献类型：
--
作者：
S. Zundler;E. Becker;M. Spocinska;Monique Slawik;Loreto Parga-Vidal;Regina Stark;Maximilian Wiendl;R. Atreya;T. Rath;M. Leppkes;K. Hildner;R. López-Posadas;S. Lukassen;A. Ekici;C. Neufert;I. Atreya;K. V. van Gisbergen;M. Neurath
虽然组织驻留记忆T细胞（TRM细胞）已被证明在感染性疾病中调节宿主保护，但其在炎症性肠病（IBD）中的功能仍有待研究。在这里，我们在人类IBD和肠道炎症实验模型中表征了TRM细胞。IBD患者粘膜中有促炎性TRM细胞积聚，CD4 + CD69 + CD103 + TRM细胞的存在预示着炎症的发展。在体内，由于适应性和先天免疫系统之间的串扰受损，在具有TRM细胞相关转录因子Hobit和Blimp-1的双敲除的小鼠中的TRM细胞的功能损伤在几种结肠炎模型中减弱疾病。最后，耗尽TRM细胞导致结肠炎活性的抑制。总之，我们的数据证明了TRM细胞在慢性肠道炎症发病机制中的核心作用，并表明这些细胞可能成为IBD未来治疗方法的靶点。
Although tissue-resident memory T cells (TRMcells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. Here we characterized TRMcells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory TRMcells accumulated in the mucosa of patients with IBD, and the presence of CD4+CD69+CD103+TRMcells was predictive of the development of flares. In vivo, functional impairment of TRMcells in mice with double knockout of the TRM-cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system. Finally, depletion of TRMcells led to a suppression of colitis activity. Together, our data demonstrate a central role for TRMcells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.