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.
【저자키워드】 COVID-19, FOXP3, Tregs, tumor Tregs, 【초록키워드】 severe COVID-19, Antiviral, IL-6, outcomes, proinflammatory, Convalescent patients, Regulatory T cell, Patient, Immune homeostasis, Complication, phenotype, Severe patient, expression, T cell response, Treg, Inflammatory response, severe disease, detrimental, similarity, Perturbation, transcription factor, dysfunction, proportions, severe COVID-19 patients, poor prognosis, excessive inflammation, perturbations, proinflammatory mediators, hallmark, COVID-19 pathology, overexpression, effectors, MOST, IL-18, transcriptomic, T regulatory cell, responses, immunological, transcriptional, responsible, resulting, proportion, the disease, contribute, increase in, suppress, notable, these cell, proinflammatory molecule, Significance, 【제목키워드】 severity, Treg, Perturbation, with COVID-19,