Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice

Background: systemic lupus erythematosus (sle) is a prototypical autoimmune disease marked by both b and t cell hyperactivity which commonly affects the joints,skin,kidneys,and brain. neuropsychiatric disease affects about 40 % of sle patients,most frequently manifesting as depression,memory deficits,and general cognitive decline. one important and yet unresolved question is whether neuropsychiatric sle (npsle) is a complication of systemic autoimmunity or whether it is primarily driven by brain-intrinsic factors. methods: to dissect the relative contributions of the central nervous system from those of the hematopoietic compartment,we generated bone marrow chimeras between healthy control (mrl/+) and lupus-prone mrl/tnfrsf6 lpr/lpr mice (mrl/+ → mrl/lpr),as well as control chimeras. after bone marrow reconstitution,mice underwent extensive behavioral testing,analysis of brain tissue,and histological assessment. results: despite transfer of healthy mrl/+ bone marrow and marked attenuation of systemic disease,we found that mrl/+ → mrl/lpr mice had a behavioral phenotype consisting of depressive-like behavior and visuospatial memory deficits,comparable to mrl/lpr → mrl/lpr control transplanted mice and the behavioral profile previously established in mrl/lpr mice. moreover,mrl/+ → mrl/lpr chimeric mice displayed increased brain rantes expression,neurodegeneration,and cellular infiltration in the choroid plexus,as well as blood brain barrier disruption,all in the absence of significant systemic autoimmunity. conclusions: chimeric mrl/+ → mrl/lpr mice displayed no attenuation of the behavioral phenotype found in mrl/lpr mice,despite normalized serum autoantibodies and conserved renal function. therefore,neuropsychiatric disease in the mrl/lpr lupus-prone strain of mice can occur absent any major contributions from systemic autoimmunity. © 2015 stock et al.