TY - JOUR T1 - Distinct signals and immune cells drive liver pathology and glomerulonephritis in ABIN1[D485N] mice JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900533 VL - 2 IS - 6 SP - e201900533 AU - Sambit Kumar Nanda AU - Tsvetana Petrova AU - Francesco Marchesi AU - Marek Gierlinski AU - Momchil Razsolkov AU - Katherine L Lee AU - Stephen W Wright AU - Vikram R Rao AU - Philip Cohen AU - J Simon C Arthur Y1 - 2019/12/01 UR - https://www.life-science-alliance.org/content/2/6/e201900533.abstract N2 - We report that TLR7, IL-6, and the adaptive immune system are essential for autoimmunity and glomerulonephritis but not for liver pathology in mice expressing the ubiquitin-binding–defective ABIN1[D485N] mutant. The blood and organs of ABIN1[D485N] mice have exceptionally high numbers of patrolling monocytes (pMo), which develop independently of IL-6 and the adaptive immune system. They are detectable in the blood months before autoimmunity and organ pathology are seen and may have diagnostic potential. The splenic pMo, inflammatory monocytes (iMo), and neutrophils of ABIN1[D485N] mice expressed high levels of mRNAs encoding proteins released during NETosis, which together with the high numbers of monocyte-derived dendritic cells (MoDCs) may drive the liver pathology in ABIN1[D485N] mice, and contribute to the pathology of other organs. The splenic iMo of ABIN1[D485N] mice displayed high expression of mRNAs encoding proteins controlling cell division and were actively dividing; this may underlie the increased pMo and MoDC numbers, which are derived from iMo. An orally active IRAK4 inhibitor suppressed all facets of the disease phenotype and prevented the increase in pMo numbers. ER -