Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation

Kaori Sakuishi, Shinji Oki, Manabu Araki, Steven A. Porcelli, Sachiko Miyake, Takashi Yamamura

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Although invariant NKT (iNKT) cells play a regulatory role in the pathogenesis of autoimmune diseases and allergy, an initial trigger for their regulatory responses remains elusive. In this study, we report that a proportion of human CD4+ iNKT cell clones produce enormous amounts of IL-5 and IL-13 when cocultured with CD1d+ APC in the presence of IL-2. Such IL-5 bias was never observed when we stimulated the same clones with α-galactosylceramide or anti-CD3 Ab. Suboptimal TCR stimulation by platebound anti-CD3 Ab was found to mimic the effect of CD1d+ APC, indicating the role of TCR signaling for selective induction of IL-5. Interestingly, DNA microarray analysis identified IL-5 and IL-13 as the most highly up-regulated genes, whereas other cytokines produced by iNKT cells, such as IL-4 and IL-10, were not significantly induced. Moreover, iNKT cells from BALB/c mice showed similar IL-5 responses after stimulation with IL-2 ex vivo or in vivo. The iNKT cell subset producing IL-5 and IL-13 could play a major role in the development of allergic disease or asthma and also in the immune regulation of Th1 inflammation.

Original languageEnglish (US)
Pages (from-to)3452-3462
Number of pages11
JournalJournal of Immunology
Volume179
Issue number6
DOIs
StatePublished - Sep 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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