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

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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
StatePublished - Sep 15 2007

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Natural Killer T-Cells
Interleukin-5
Inflammation
Interleukin-13
Interleukin-2
Clone Cells
Galactosylceramides
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Interleukin-4
Interleukin-10
Autoimmune Diseases
Hypersensitivity
Asthma
Cytokines
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Sakuishi, K., Oki, S., Araki, M., Porcelli, S. A., Miyake, S., & Yamamura, T. (2007). Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. Journal of Immunology, 179(6), 3452-3462.

Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. / Sakuishi, Kaori; Oki, Shinji; Araki, Manabu; Porcelli, Steven A.; Miyake, Sachiko; Yamamura, Takashi.

In: Journal of Immunology, Vol. 179, No. 6, 15.09.2007, p. 3452-3462.

Research output: Contribution to journalArticle

Sakuishi, K, Oki, S, Araki, M, Porcelli, SA, Miyake, S & Yamamura, T 2007, 'Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation', Journal of Immunology, vol. 179, no. 6, pp. 3452-3462.
Sakuishi K, Oki S, Araki M, Porcelli SA, Miyake S, Yamamura T. Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. Journal of Immunology. 2007 Sep 15;179(6):3452-3462.
Sakuishi, Kaori ; Oki, Shinji ; Araki, Manabu ; Porcelli, Steven A. ; Miyake, Sachiko ; Yamamura, Takashi. / Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. In: Journal of Immunology. 2007 ; Vol. 179, No. 6. pp. 3452-3462.
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