The Src family tyrosine kinase Fyn regulates natural killer T cell development.
T lymphocytes express two Src tyrosine kinases, Lck and Fyn. While thymocyte and T cell subsets are largely normal in fyn(-/-) mice, animals lacking Lck have impaired T cell development. Here, it is shown that Fyn is required for the rapid burst of interleukin (IL)-4 and IL-13 synthesis, which occurs promptly after T cell receptor activation. The lack of cytokine induction in fyn mutant mice is due to a block in natural killer (NK) T cell development. Studies using bone marrow chimeras indicate that the defect behaves in a cell-autonomous manner, and the lack of NK T cells is probably not caused by inappropriate microenvironmental cues. Both NK T cells and conventional T cells express similar levels of Lck, implying that Fyn and Lck have distinct roles in regulating NK T cell ontogeny. The fyn mutation defines the first signaling molecule that is selectively required for NK T cell, but not for T lymphocyte or NK cell development.
Gadue
P
P
Graduate Program in Immunology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Morton
N
N
Stein
P L
PL
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D015321:Gene Rearrangement / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics* / Q000276:immunology
D017252:CD3 Complex; D018793:Interleukin-13; D011518:Proto-Oncogene Proteins; D015847:Interleukin-4; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases