IL-6 receptor α defines effector memory CD81 T cells producing Th2 cytokines and expanding in asthma

Naeun Lee, Sungyong You, Min Sun Shin, Won Woo Lee, Ki Soo Kang, Sang Hyun Kim, Wan Uk Kim, Robert J. Homer, Min Jong Kang, Ruth R. Montgomery, Charles S.Dela Cruz, Albert C. Shaw, Patty J. Lee, Geoffrey L. Chupp, Daehee Hwang, Insoo Kang

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 languageEnglish
Pages (from-to)1383-1394
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume190
Issue number12
DOIs
StatePublished - 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

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