4.6 Article

The Aryl Hydrocarbon Receptor Modulates T Follicular Helper Cell Responses to Influenza Virus Infection in Mice

期刊

JOURNAL OF IMMUNOLOGY
卷 208, 期 10, 页码 2319-+

出版社

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2100936

关键词

-

资金

  1. U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH) [R01ES030300, R01ES004862, P30ES01247, T32AI007285]
  2. HHS, NIH, National Institute of Environmental Health Sciences [F31ES032301]

向作者/读者索取更多资源

This study demonstrates that activation of the aryl hydrocarbon receptor (AHR) reduces the frequency and differentiation of T follicular helper (Tfh) cells during viral infection. It also affects T cell-dependent B cell responses and alters the balance between Tfollicular regulatory (Tfr) cells and Tfh cells. These findings have important implications for understanding the role of environmental factors in immune defenses against viral pathogens.
T follicular helper (Tfh) cells support Ab responses and are a critical component of adaptive immune responses to respiratory viral infections. Tfh cells are regulated by a network of signaling pathways that are controlled, in part, by transcription factors. The aryl hydrocarbon receptor (AHR) is an environment-sensing transcription factor that modulates many aspects of adaptive immunity by binding a range of small molecules. However, the contribution of AHR signaling to Tfh cell differentiation and function is not known. In this article, we report that AHR activation by three different agonists reduced the frequency of Tfh cells during primary infection of C57BL/6 mice with influenza A virus (IAV). Further, using the high-affinity and AHR-specific agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin, we show that AHR activation reduced Tfh cell differentiation and T cell-dependent B cell responses. Using conditional AHR knockout mice, we demonstrated that alterations of Tfh cells and T cell-dependent B cell responses after AHR activation required the AHR in T cells. AHR activation reduced the number of T follicular regulatory (Tfr) cells; however, the ratio of Tfr to Tfh cells was amplified. These alterations to Tfh and Tfr cells during IAV infection corresponded with differences in expression of BCL6 and FOXP3 in CD4(+) T cells and required the AHR to have a functional DNA-binding domain. Overall, these findings support that the AHR modulates Tfh cells during viral infection, which has broad-reaching consequences for understanding how environmental factors contribute to variation in immune defenses against infectious pathogens, such as influenza and severe acute respiratory syndrome coronavirus.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据