Diacylglycerol kinase zeta positively controls the development of iNKT-17 cells.
Invariant natural killer T (iNKT) cells play important roles in bridging innate and adaptive immunity via rapidly producing a variety of cytokines. A small subset of iNKT cells produces IL-17 and is generated in the thymus during iNKT-cell ontogeny. The mechanisms that control the development of these IL-17-producing iNKT-17 cells (iNKT-17) are still not well defined. Diacylglycerol kinase ζ (DGKζ) belongs to a family of enzymes that catalyze the phosphorylation and conversion of diacylglycerol to phosphatidic acid, two important second messengers involved in signaling from numerous receptors. We report here that DGKζ plays an important role in iNKT-17 development. A deficiency of DGKζ in mice causes a significant reduction of iNKT-17 cells, which is correlated with decreased RORγt and IL-23 receptor expression. Interestingly, iNKT-17 defects caused by DGKζ deficiency can be corrected in chimeric mice reconstituted with mixed wild-type and DGKζ-deficient bone marrow cells. Taken together, our data identify DGKζ as an important regulator of iNKT-17 development through iNKT-cell extrinsic mechanisms.
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, North Carolina, United States of America ; Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jinhong
J
Wu
Shudan
S
Shen
Jialong
J
Yang
Zhenwei
Z
Xia
Xiao-Ping
XP
Zhong
D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019852:Diacylglycerol Kinase / Q000502:physiology*; D004075:Diglycerides / Q000378:metabolism; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000201:enzymology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism
C011439:1,2-diacylglycerol; D004075:Diglycerides; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010712:Phosphatidic Acids; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018123:Receptors, Interleukin; C528688:interleukin-23 receptor, mouse; D019852:Diacylglycerol Kinase; C512480:diacylglycerol kinase zeta, mouse