期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：37
DOI：10.1073/pnas.2111315118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Regulatory T cells (Tregs) are responsible for restraining excessive inflammation, a hallmark of COVID-19. We identified a striking phenotype in Tregs from patients with severe disease, as well as an interesting role for interleukin (IL)-6 and IL-18. An increased suppressive profile, including increased Treg proportions, combined with the expression of proinflammatory mediators, distinguished severe patients and persisted in some of those recovered. This phenotype is in notable similarity to that found in tumor-infiltrating Tregs, which are generally associated with poor prognosis, and suggests both a detrimental role for these cells in COVID-19 as well as a potential explanation for some of the still largely unexplored complications associated with recovery.
The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3
+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19–linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.
