RRC ID 43477
Author Diao H, Iwabuchi K, Li L, Onoe K, Van Kaer L, Kon S, Saito Y, Morimoto J, Denhardt DT, Rittling S, Uede T.
Title Osteopontin regulates development and function of invariant natural killer T cells.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract Invariant natural killer T (iNKT) cells belong to a subset of lymphocytes bridging innate and acquired immunity. We demonstrated that osteopontin (OPN) is involved in the activation of iNKT cells. In the present work, we examined whether OPN affects development and function of iNKT cells. We found that the number of peripheral iNKT cells was significantly reduced in OPN-deficient mice compared with wild-type mice. Although the number of thymic iNKT cells was not different between WT and OPN-deficient mice, intrathymic iNKT cell maturation was impaired in OPN-deficient mice. iNKT cell function was also significantly altered in OPN-deficient mice, as evidenced by (i) deficient down-regulation of iNKT cell receptor, (ii) reduction of IL-4 production while preserving production of IFN-gamma, and (iii) reduction of Fas ligand (FasL) expression, leading to reduced Fas/FasL-dependent cytotoxicity against hepatocytes. Importantly, activation of the transcription factors NFAT2 (nuclear factor of activated T cells 2) and GATA-3 was impaired, whereas activation of T-bet was preserved in iNKT cells of OPN-deficient mice. These data collectively indicate that OPN plays a pivotal role not only in the development, but also in the function of iNKT cells.
Volume 105(41)
Pages 15884-9
Published 2008-10-14
DOI 10.1073/pnas.0806089105
PII 0806089105
PMID 18836077
PMC PMC2560993
MeSH Animals Down-Regulation Fas Ligand Protein Interleukin-4 Killer Cells, Natural / metabolism* Killer Cells, Natural / physiology Lymphocyte Activation* Mice Mice, Knockout Osteopontin / deficiency Osteopontin / physiology* Receptors, KIR Thymus Gland / immunology Transcription Factors
IF 9.504
Times Cited 22
Human and Animal Cells