Osteopontin regulates development and function of invariant natural killer T cells.
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.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, Zhejiang 310003, China. diao.hy@163.com
Hongyan
H
Diao
Kazuya
K
Iwabuchi
Lanjuan
L
Li
Kazunori
K
Onoe
Luc
L
Van Kaer
Shigeyuki
S
Kon
Yoshinari
Y
Saito
Junko
J
Morimoto
David T
DT
Denhardt
Susan
S
Rittling
Toshimitsu
T
Uede
D000818:Animals; D015536:Down-Regulation; D053222:Fas Ligand Protein; D015847:Interleukin-4; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin / Q000172:deficiency / Q000502:physiology*; D054340:Receptors, KIR; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors
D053222:Fas Ligand Protein; D054340:Receptors, KIR; D014157:Transcription Factors; D053495:Osteopontin; D015847:Interleukin-4