Open AccessProfound Treg perturbations correlate with COVID-19 severity
Author(s) -
Silvia Galván-Peña,
Juliette Léon,
Kaitavjeet Chowdhary,
Daniel A. Michelson,
Brinda Vijaykumar,
Liang Yang,
Angela M. Magnuson,
Felicia Chen,
Zachary Manickas-Hill,
Alicja Piechocka-Trocha,
Daniel Worrall,
Kathryn Hall,
Musie Ghebremichael,
Bruce D. Walker,
Jonathan Z. Li,
Xu G. Yu,
Diane Mathis,
Christophe Benoist
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2111315118
Subject(s) - phenotype , proinflammatory cytokine , immunology , covid-19 , inflammation , disease , biology , medicine , virology , gene , genetics , infectious disease (medical specialty) , outbreak
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.