A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage
Pristane causes chronic peritoneal inflammation resulting in lupus, which in C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage (DAH). Mineral oil (MO) also causes inflammation, but not lupus or DAH. Since monocyte depletion prevents DAH, we examined the role of...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/76205 |
| _version_ | 1798028744944779264 |
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| author | Shuhong Han Haoyang Zhuang Rawad Daniel Arja Westley H Reeves |
| author_facet | Shuhong Han Haoyang Zhuang Rawad Daniel Arja Westley H Reeves |
| author_sort | Shuhong Han |
| collection | DOAJ |
| description | Pristane causes chronic peritoneal inflammation resulting in lupus, which in C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage (DAH). Mineral oil (MO) also causes inflammation, but not lupus or DAH. Since monocyte depletion prevents DAH, we examined the role of monocytes in the disease. Impaired bone marrow (BM) monocyte egress in Ccr2−/− mice abolished DAH, confirming the importance of monocyte recruitment to the lung. Circulating Ly6Chi monocytes from pristane-treated mice exhibited increased annexin-V staining in comparison with MO-treated controls without evidence of apoptosis, suggesting that pristane alters the distribution of phosphatidylserine in the plasma membrane before or shortly after monocyte egress from the BM. Plasma membrane asymmetry also was impaired in Nr4a1-regulated Ly6Clo/− ‘patrolling’ monocytes, which are derived from Ly6Chi precursors. Patrolling Ly6Clo/− monocytes normally promote endothelial repair, but their phenotype was altered in pristane-treated mice. In contrast to MO-treated controls, Nr4a1-regulated Ly6Clo/− monocytes from pristane-treated mice were CD138+, expressed more TremL4, a protein that amplifies TLR7 signaling, and exuberantly produced TNFα in response to TLR7 stimulation. TremL4 expression on these novel CD138+ monocytes was regulated by Nr4a1. Thus, monocyte CD138, high TremL4 expression, and annexin-V staining may define an activated/inflammatory subtype of patrolling monocytes associated with DAH susceptibility. By altering monocyte development, pristane exposure may generate activated Ly6Chi and Ly6Clo/− monocytes, contributing to lung microvascular endothelial injury and DAH susceptibility. |
| first_indexed | 2024-04-11T19:13:21Z |
| format | Article |
| id | doaj.art-5f0c01bfa91e45358b45d2d0b13d8132 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T19:13:21Z |
| publishDate | 2022-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5f0c01bfa91e45358b45d2d0b13d81322022-12-22T04:07:30ZengeLife Sciences Publications LtdeLife2050-084X2022-10-011110.7554/eLife.76205A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhageShuhong Han0https://orcid.org/0000-0002-6951-120XHaoyang Zhuang1Rawad Daniel Arja2https://orcid.org/0000-0003-4555-2098Westley H Reeves3https://orcid.org/0000-0002-2924-4549Division of Rheumatology, Allergy, & Clinical Immunology, University of Florida, Gainesville, United StatesDivision of Rheumatology, Allergy, & Clinical Immunology, University of Florida, Gainesville, United StatesDivision of Rheumatology, Allergy, & Clinical Immunology, University of Florida, Gainesville, United StatesDivision of Rheumatology, Allergy, & Clinical Immunology, University of Florida, Gainesville, United StatesPristane causes chronic peritoneal inflammation resulting in lupus, which in C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage (DAH). Mineral oil (MO) also causes inflammation, but not lupus or DAH. Since monocyte depletion prevents DAH, we examined the role of monocytes in the disease. Impaired bone marrow (BM) monocyte egress in Ccr2−/− mice abolished DAH, confirming the importance of monocyte recruitment to the lung. Circulating Ly6Chi monocytes from pristane-treated mice exhibited increased annexin-V staining in comparison with MO-treated controls without evidence of apoptosis, suggesting that pristane alters the distribution of phosphatidylserine in the plasma membrane before or shortly after monocyte egress from the BM. Plasma membrane asymmetry also was impaired in Nr4a1-regulated Ly6Clo/− ‘patrolling’ monocytes, which are derived from Ly6Chi precursors. Patrolling Ly6Clo/− monocytes normally promote endothelial repair, but their phenotype was altered in pristane-treated mice. In contrast to MO-treated controls, Nr4a1-regulated Ly6Clo/− monocytes from pristane-treated mice were CD138+, expressed more TremL4, a protein that amplifies TLR7 signaling, and exuberantly produced TNFα in response to TLR7 stimulation. TremL4 expression on these novel CD138+ monocytes was regulated by Nr4a1. Thus, monocyte CD138, high TremL4 expression, and annexin-V staining may define an activated/inflammatory subtype of patrolling monocytes associated with DAH susceptibility. By altering monocyte development, pristane exposure may generate activated Ly6Chi and Ly6Clo/− monocytes, contributing to lung microvascular endothelial injury and DAH susceptibility.https://elifesciences.org/articles/76205CD138+ monocyteNR4A1pristane |
| spellingShingle | Shuhong Han Haoyang Zhuang Rawad Daniel Arja Westley H Reeves A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage eLife CD138+ monocyte NR4A1 pristane |
| title | A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage |
| title_full | A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage |
| title_fullStr | A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage |
| title_full_unstemmed | A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage |
| title_short | A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage |
| title_sort | novel monocyte differentiation pattern in pristane induced lupus with diffuse alveolar hemorrhage |
| topic | CD138+ monocyte NR4A1 pristane |
| url | https://elifesciences.org/articles/76205 |
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