Deficiency of macrophage-derived Dnase1L3 causes lupus-like phenotypes in mice.
J Leukoc Biol
; 114(6): 547-556, 2023 11 24.
Article
en En
| MEDLINE
| ID: mdl-37804110
ABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disease caused by environmental factors and loss of key proteins, including the endonuclease Dnase1L3. Dnase1L3 absence causes pediatric-onset lupus in humans, while reduced activity occurs in adult-onset SLE. The amount of Dnase1L3 that prevents lupus remains unknown. To genetically reduce Dnase1L3 levels, we developed a mouse model lacking Dnase1L3 in macrophages (conditional knockout [cKO]). Serum Dnase1L3 levels were reduced 67%, though Dnase1 activity remained constant. Homogeneous and peripheral antinuclear antibodies were detected in the sera by immunofluorescence, consistent with anti-double-stranded DNA (anti-dsDNA) antibodies. Total immunoglobulin M, total immunoglobulin G, and anti-dsDNA antibody levels increased in cKO mice with age. The cKO mice developed anti-Dnase1L3 antibodies. In contrast to global Dnase1L3-/- mice, anti-dsDNA antibodies were not elevated early in life. The cKO mice had minimal kidney pathology. Therefore, we conclude that an intermediate reduction in serum Dnase1L3 causes mild lupus phenotypes, and macrophage-derived DnaselL3 helps limit lupus.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
Lupus Eritematoso Sistémico
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Animals
/
Child
/
Humans
Idioma:
En
Revista:
J Leukoc Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos