@article{9919d1e8c89742fbbc2bd2ce8244b3ca,
title = "A Novel Microglia-Specific Transcriptional Signature Correlates With Behavioral Deficits in Neuropsychiatric Lupus",
abstract = "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.",
keywords = "DAM, NP-SLE, SLE, behavior, interferon, lupus, microglia",
author = "Makinde, {Hadijat M.} and Winter, {Deborah R.} and Daniele Procissi and Mike, {Elise V.} and Stock, {Ariel D.} and Kando, {Mary J.} and Gadhvi, {Gaurav T.} and Steven Droho and Bloomfield, {Christina L.} and Dominguez, {Salina T.} and Mayr, {Maximilian G.} and Lavine, {Jeremy A.} and Chaim Putterman and Cuda, {Carla M.}",
note = "Funding Information: This work was supported by the Northwestern University Behavioral Phenotyping Core, Center for Translational Imaging, Next Generation Sequencing Core, and the Northwestern University - Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553). Flow Cytometry Cell Sorting was performed on a BD FACSAria SORP system, purchased through the support of NIH 1S10OD011996-01. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory which is supported by NCI P30-CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Funding. These studies were supported by training grants from the NIH to HM (T32-AR007611) and EM (T32-GM007288); a NIH Research Supplement to Promote Diversity in Health-Related Research (3R01AR065594-02W1) to EM; a R01 grant (3R01AR065594) to CP and a K01 grant (5K01AR060169) to CC from the National Institute of Arthritis and Musculoskeletal Diseases; a Novel Research grant from the Lupus Research Alliance to CC (637405). Funding Information: These studies were supported by training grants from the NIH to HM (T32-AR007611) and EM (T32-GM007288); a NIH Research Supplement to Promote Diversity in Health-Related Research (3R01AR065594-02W1) to EM; a R01 grant (3R01AR065594)",
year = "2020",
month = feb,
day = "26",
doi = "10.3389/fimmu.2020.00230",
language = "English (US)",
volume = "11",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}