TY - JOUR
T1 - Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation
AU - Sakuishi, Kaori
AU - Oki, Shinji
AU - Araki, Manabu
AU - Porcelli, Steven A.
AU - Miyake, Sachiko
AU - Yamamura, Takashi
PY - 2007/9/15
Y1 - 2007/9/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.179.6.3452
DO - 10.4049/jimmunol.179.6.3452
M3 - Article
C2 - 17785779
AN - SCOPUS:35748932380
SN - 0022-1767
VL - 179
SP - 3452
EP - 3462
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -