Nanda, S. K., Petrova, T., Marchesi, F. , Gierlinski, M., Razsolkov, M., Lee, K. L., Wright, S. W., Rao, V. R., Cohen, P. and Arthur, J. S. C. (2019) Distinct signals and immune cells drive liver pathology and glomerulonephritis in ABIN1[D485N] mice. Life Science Alliance, 2(6), e201900533. (doi: 10.26508/lsa.201900533) (PMID:31694920)
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Abstract
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.
| Item Type: | Articles |
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| Additional Information: | The research conducted by SK Nanda, T Petrova, F Marchesi, and M Gierlinski was funded by grants from the UK Medical Research Council (MR/R021406/1) (to P Cohen and JSC Arthur) and the Wellcome Trust (209380/Z/17/Z) (to P Cohen). Some of the studies were carried out while T Petrova was the recipient of a Wellcome Trust Prize Studentship (105309/Z/14/Z). M Razsolkov holds a UK Medical Research Council studentship (MR/N013735/1). The work performed by VR Rao, K Lee, and SW Wright was funded by the Research & Development budget of Pfizer Inc. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Marchesi, Dr Francesco |
| Authors: | Nanda, S. K., Petrova, T., Marchesi, F., Gierlinski, M., Razsolkov, M., Lee, K. L., Wright, S. W., Rao, V. R., Cohen, P., and Arthur, J. S. C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Life Science Alliance |
| Publisher: | Life Science Alliance |
| ISSN: | 2575-1077 |
| ISSN (Online): | 2575-1077 |
| Published Online: | 06 November 2019 |
| Copyright Holders: | Copyright © 2019 Nanda et al. |
| First Published: | First published in Life Science Alliance 2(6):e201900533 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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