Immune-Mediated Nephropathy and Systemic Autoimmunity in Mice Does Not Require Receptor Interacting Protein Kinase 3 (RIPK3).
Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates. A second pathway mediating necrosis involves Receptor-Interacting Serine-Threonine Kinase 3 (RIPK3); in this study we sought to investigate the impact of RIPK3 on the development of lupus and nephritis in both sexes. To this end, we used two inducible murine models of lupus: chronic graft versus host disease (cGvHD) and pristane-induced lupus; and nephrotoxic serum (NTS)-induced nephritis as a model of immune mediated nephropathy. We found that the absence of RIPK3 has neither positive nor negative impact on the disease development or progression of lupus and nephritis in all three models, and in both male and female mice. We conclude that RIPK3 is dispensable for the pathogenesis of lupus and immune mediated nephropathy as to accelerate, worsen or ameliorate the disease.
Department of Medicine/Rheumatology Section, Lewis Katz School of Medicine, Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, United States of America.
Chelsea
C
Corradetti
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States of America.
Neelakshi R
NR
Jog
Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, United States of America.
Stefania
S
Gallucci
Department of Medicine, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA, 30912, United States of America.
Michael
M
Madaio
Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, United States of America.
Siddharth
S
Balachandran
Department of Medicine/Rheumatology Section, Lewis Katz School of Medicine, Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, United States of America.
Roberto
http://orcid.org/0000-0002-1379-1118
R
Caricchio
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