The cell cycle inhibitor p21 controls T-cell proliferation and sex-linked lupus development.
Here we show that the cell-cycle regulator p21 is involved in immune system function. T lymphocytes from p21-/- mice exhibit significant proliferative advantage over wild-type cells following prolonged stimulation, but not after primary activation. Consistent with this, p21-deficient mice accumulate abnormal amounts of CD4+ memory cells, and develop loss of tolerance towards nuclear antigens. Similar to human lupus, female p21-deficient mice develop antibodies against dsDNA, lymphadenopathy, and glomerulonephritis, leading to decreased viability. These data demonstrate a specialized role for p21 in the control of T-cell proliferation, tolerance to nuclear antigens, and female-prone lupus. These findings could be the basis for new therapeutic approaches to lupus.
Balomenos
D
D
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Cantoblanco, E-28049 Madrid, Spain.
Martín-Caballero
J
J
García
M I
MI
Prieto
I
I
Flores
J M
JM
Serrano
M
M
Martínez-A
C
C
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D002455:Cell Division / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D004247:DNA / Q000276:immunology; D005260:Female; D008040:Genetic Linkage; D005921:Glomerulonephritis / Q000276:immunology; D007156:Immunologic Memory; D008177:Lupus Vulgaris / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012737:Sex Factors; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D000974:Antibodies, Antinuclear; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004247:DNA