| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
24 Invariant NKT Cells1
* Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Osaka, Japan;
Department of Oncology, Chinese PLA General Hospital, Beijing, China;
Department of Anesthesiology,
Department of Obstetrics and Gynecology,
¶ Department of Molecular Biology, and
|| Department of Biomedical Research Center, Division of Analytical Science, Faculty of Medicine, Saitama Medical University, Saitama, Japan;
# Section on Immunology and Immunogenetics, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215; and
** Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
CD1d-restricted invariant NKT (iNKT) cells play crucial roles in various types of immune responses, including autoimmune diseases, infectious diseases and tumor surveillance. The mechanisms underlying their adjuvant functions are well understood. Nevertheless, although IL-4 and IL-10 production characterize iNKT cells able to prevent or ameliorate some autoimmune diseases and inflammatory conditions, the precise mechanisms by which iNKT cells exert immune regulatory function remain elusive. This study demonstrates that the activation of human iNKT cells by their specific ligand 
-galactosylceramide enhances IL-12p70 while inhibiting the IL-23 production by monocyte-derived dendritic cells, and in turn down-regulating the IL-17 production by memory CD4+ Th cells. The ability of the iNKT cells to regulate the differential production of IL-12p70/IL-23 is mainly mediated by a remarkable hallmark of their function to produce both Th1 and Th2 cytokines. In particular, the down-regulation of IL-23 is markedly associated with a production of IL-4 and IL-10 from iNKT cells. Moreover, Th2 cytokines, such as IL-4 and IL-13 play a crucial role in defining the biased production of IL-12p70/IL-23 by enhancement of IL-12p70 in synergy with IFN-
, whereas inhibition of the IFN--promoted IL-23 production. Collectively, the results suggest that iNKT cells modify the IL-12p70/IL-23 balance to enhance the IL-12p70-induced cell-mediated immunity and suppress the IL-23-dependent inflammatory pathologies. These results may account for the long-appreciated contrasting beneficial and adverse consequence of ligand activation of iNKT cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Grants-in-Aid 21710069, 21791572, 21791473, 21791958, 21602005, 21591251, 20591158, 20591190, 19890205, 19790637, and 18790689 from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by research grants from the 21st Century Center of Excellence Program, Ministry of Education, Mitsubishi Pharma Research Foundation (05), Takeda Science Foundation (05), Ochiai Memorial Award (07, 08), Ichiro Kanehara Foundation (08), Kanzawa Medical Research Foundation (09), and Kowa Life Science Foundation (09).
2 Y.U., T.-Y.L., Y.N., and M.S. contributed equally to this study as lead authors.
3 Address correspondence and reprint requests to Dr. Yasushi Uemura, Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Moriguchi, Osaka, 570-8506, Japan. E-mail address: uemuraya{at}takii.kmu.ac.jp
4 Abbreviations used in this paper: iNKT, invariant NKT; -GalCer, -galactosylceramide; DN, double negative; DC, dendritic cell; rh, recombinant human; SEB, staphylococcal enterotoxin B.
5 The online version of this article contains supplemental material.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
