Abstract
Rationale: Cytokine receptors can be markers defining different T-cell subsets and considered as therapeutic targets. The association of IL-6 and IL-6 receptor a (IL-6Rα) with asthma was reported, suggesting their involvement in asthma.
Objectives: To determine whether and how IL-6Rα defines a distinct effector memory (EM) CD81 T-cell population in health and disease.
Methods: EM CD81 T cells expressing IL-6Rα (IL-6Rαhigh) were identified in human peripheral blood and analyzed for function, gene, and transcription factor expression. The relationship of these cells with asthma was determined using blood and sputum. Measurements and Main Results: A unique population of IL-6Rαhigh EM CD81 T cells was found in peripheral blood. These cells that potently proliferated, survived, and produced high levels of the Th2-type cytokines IL-5 and IL-13 had increased levels of GATA3 and decreased levels of T-bet and Blimp-1 in comparison with other EM CD81 T cells. In fact, GATA3 was required for IL-6Rα expression. Patients with asthma had an increased frequency of IL-6Rαhigh EM CD81 T cells in peripheral blood compared with healthy control subjects. Also, IL-6Rαhigh EM CD81 T cells exclusively produced IL-5 and IL-13 in response to asthma-associated respiratory syncytial virus and bacterial superantigens.
Conclusions: Human IL-6Rαhigh EM CD81 T cells is a unique cell subset that may serve as a reservoir for effector CD81 T cells, particularly the ones producing Th2-type cytokines, and expand in asthma.
Original language | English |
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Pages (from-to) | 1383-1394 |
Number of pages | 12 |
Journal | American Journal of Respiratory and Critical Care Medicine |
Volume | 190 |
Issue number | 12 |
DOIs | |
State | Published - 15 Dec 2014 |
Bibliographical note
Publisher Copyright:Copyright © 2014 by the American Thoracic Society.
Keywords
- Asthma
- CD81 T cells
- Human
- IL-6 receptor
- Th2 cytokines