International Immunology, Vol. 14, No. 7, pp. 695-700,
July 2002
© 2002 Japanese Society for Immunology
Endotoxin can induce MyD88-deficient dendritic cells to support Th2 cell differentiation
1 Department of Host Defense and 5 Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan 2 SORST, Japan Science and Technology Corporation, Osaka 565-0871, Japan 3 RIKEN Research Center for Allergy and Immunology, Osaka 565-0871, Japan 4 Department of Obstetrics and Gynecology, Tottori University, School of Medicine, Yonago 683-8503, Japan
Correspondence to: S. Akira; E-mail: sakira{at}biken.osaka-u.ac.jp
Transmitting editor: S. Koyasu
Toll-like receptor (TLR) signaling activates dendritic cells (DC) to secrete proinflammatory cytokines and up-regulate co-stimulatory molecule expression, thereby linking innate and adaptive immunity. A TLR-associated adapter protein, MyD88, is essential for cytokine production induced by TLR. However, in response to a TLR4 ligand, lipopolysaccharide (LPS), MyD88-deficient (MyD88–/–) DC can up-regulate co-stimulatory molecule expression and enhance their T cell stimulatory activity, indicating that the MyD88-independent pathway through TLR4 can induce some features of DC maturation. In this study, we have further characterized function of LPS-stimulated, MyD88–/– DC. In response to LPS, wild-type DC could enhance their ability to induce IFN-
production in allogeneic mixed lymphocyte reaction (alloMLR). In contrast, in response to LPS, MyD88–/– DC augmented their ability to induce IL-4 instead of IFN- in alloMLR. Impaired production of Th1-inducing cytokines in MyD88–/– DC cannot fully account for their increased Th2 cell-supporting ability, because absence of Th1-inducing cytokines in DC caused impairment of IFN-, but did not lead to augmentation of IL-4 production in alloMLR. In vivo experiments with adjuvants also revealed Th2-skewed immune responses in MyD88–/– mice. These results demonstrate that the MyD88-independent pathway through TLR4 can confer on DC the ability to support Th2 immune responses.
Keywords: dendritic cells, innate immunity, lipopolysaccharide, Th1, Th2, Toll-like receptor
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