PMID- 32174913 OWN - NLM STAT- MEDLINE VI - 11 TI - A Novel Microglia-Specific Transcriptional Signature Correlates With Behavioral Deficits in Neuropsychiatric Lupus. PG - 230 CI - Copyright © 2020 Makinde, Winter, Procissi, Mike, Stock, Kando, Gadhvi, Droho, Bloomfield, Dominguez, Mayr, Lavine, Putterman and Cuda. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 IS - 1664-3224 (Electronic) LID - 10.3389/fimmu.2020.00230 [doi] FAU - Makinde, Hadijat M AU - Makinde HM AD - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Winter, Deborah R AU - Winter DR AD - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Procissi, Daniele AU - Procissi D AD - Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Mike, Elise V AU - Mike EV AD - Division of Rheumatology, Department of Medicine, Albert Einstein College of Medicine, The Bronx, NY, United States. FAU - Stock, Ariel D AU - Stock AD AD - Division of Rheumatology, Department of Medicine, Albert Einstein College of Medicine, The Bronx, NY, United States. FAU - Kando, Mary J AU - Kando MJ AD - Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Gadhvi, Gaurav T AU - Gadhvi GT AD - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Droho, Steven AU - Droho S AD - Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Bloomfield, Christina L AU - Bloomfield CL AD - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Dominguez, Salina T AU - Dominguez ST AD - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Mayr, Maximilian G AU - Mayr MG AD - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Lavine, Jeremy A AU - Lavine JA AD - Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. FAU - Putterman, Chaim AU - Putterman C AD - Division of Rheumatology, Department of Medicine, Albert Einstein College of Medicine, The Bronx, NY, United States. AD - Research Division, Azrieli Faculty of Medicine and Galilee Medical Center, Nahariya, Israel. FAU - Cuda, Carla M AU - Cuda CM AD - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. IS - 1664-3224 (Linking) SB - IM MH - Animals MH - Association Learning MH - Blood-Brain Barrier MH - Disease Models, Animal MH - Female MH - Genetic Predisposition to Disease MH - Gray Matter/diagnostic imaging/pathology MH - Lupus Erythematosus, Systemic/*complications/genetics/immunology/pathology MH - Lupus Vasculitis, Central Nervous System/*genetics/immunology/pathology MH - Macrophages/metabolism MH - Maze Learning MH - Memory Disorders/*etiology/genetics/immunology MH - Mice MH - Mice, Inbred MRL lpr MH - Mice, Mutant Strains MH - Microglia/*metabolism MH - Morris Water Maze Test MH - Organ Size MH - Predictive Value of Tests MH - Prepulse Inhibition MH - Reflex, Startle MH - *Transcriptome MH - White Matter/diagnostic imaging/pathology OTO - NOTNLM OT - *DAM OT - *NP-SLE OT - *SLE OT - *behavior OT - *interferon OT - *lupus OT - *microglia PMC - PMC7055359 DCOM- 20210305 LR - 20210305 DP - 2020 DEP - 20200226 AB - Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) affect over one-half of SLE patients, yet underlying mechanisms remain largely unknown. We demonstrate that SLE-prone mice (CReCOM) develop NP-SLE, including behavioral deficits prior to systemic autoimmunity, reduced brain volumes, decreased vascular integrity, and brain-infiltrating leukocytes. NP-SLE microglia exhibit numerical expansion, increased synaptic uptake, and a more metabolically active phenotype. Microglia from multiple SLE-prone models express a "NP-SLE signature" unrelated to type I interferon. Rather, the signature is associated with lipid metabolism, scavenger receptor activity and downregulation of inflammatory and chemotaxis processes, suggesting a more regulatory, anti-inflammatory profile. NP-SLE microglia also express genes associated with disease-associated microglia (DAM), a subset of microglia thought to be instrumental in neurodegenerative diseases. Further, expression of "NP-SLE" and "DAM" signatures correlate with the severity of behavioral deficits in young SLE-prone mice prior to overt systemic disease. Our data are the first to demonstrate the predictive value of our newly identified microglia-specific "NP-SLE" and "DAM" signatures as a surrogate for NP-SLE clinical outcomes and suggests that microglia-intrinsic defects precede contributions from systemic SLE for neuropsychiatric manifestations.