Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Rheumatoid arthritis (RA) is an inflammatory disease of the joints associated with cardiovascular disease, which accounts for 40% of RA mortality. Macrophages are implicated in pathology of both RA and atherosclerosis, however it remains unknown if shared immune mechanisms are involved at both sites of disease. To investigate this, KRN Ag7 mice which develop spontaneous arthritis and atherosclerosis were used to monitor changes in the cellular composition of the synovium and aorta during development of disease. To further characterize the role of monocyte and macrophage populations, CCR2-/- mice, which have reduced Ly6chi monocytes and impaired macrophage recruitment, were crossed with KRN Ag7 mice to create KRN Ag7 CCR2-/-.
KRN Ag7, C57Bl/6, and KRN Ag7 CCR2-/- mice were bred in house and euthanized at desired timepoints from 1 – 24 months. Ankles and aortas were collected and single cell suspensions were prepared. Cell suspensions were stained with an antibody cocktail designed to identify monocyte and macrophage populations which were analyzed by flow cytometry. Statistical analysis was carried out in Flowjo v9 and Prism7. Statistical significance was defined at P ≤ 0.05.
KRN Ag7 mice developed arthropathy from birth. Flow cytometric analysis of synovial immune cell populations in KRN Ag7 mice from 1-24months identified two phases of disease. From 1-3 months, an inflammatory phenotype is characterized by significant increases in monocytes, eosinophils, and neutrophils and a decrease in dendritic cells, compared to C57Bl/6. During an erosive phase from 6-24months levels of these populations trended towards C57Bl/6 levels, but remained significantly different. Macrophage populations MHCII–CX3CR1+ and MHCII+CX3CR1– were associated with the inflammation phase and were significantly increased and decreased respectively compared to C57Bl/6. KRNAg7 CCR2-/- mice developed comparable arthropathy to KRN Ag7 mice from birth, although levels of total CD11b+ cells, neutrophils and monocytes were all significantly lower in KRN Ag7 CCR2-/-synovium than in KRN Ag7. Composition of the macrophage compartment of KRN Ag7 and KRN Ag7 CCR2-/- mice displayed similar trends including an increased and decreased proportions of MHCII–CX3CR1+ and MHCII+CX3CR1– macrophages. Cell populations isolated from the aorta of KRN Ag7 CCR2-/- mice displayed a striking inflammatory phenotype from 1 month, comprising more total CD11b+ cells, neutrophils, and decreased dendritic cells than both KRN Ag7 and C57Bl/6 controls. KRN Ag7 CCR2-/- aorta also had a significant increase in monocytes, although levels of macrophages were comparable to those of C57Bl/6 controls. All trends were maintained at 3 months.
These findings suggest CCR2 is not essential for the development of inflammatory arthritis in KRN Ag7 mice, but does affect cell burden. Surprisingly, aorta tissue from KRN Ag7 CCR2-/- mice developed a more striking inflammatory phenotype than KRN Ag7. Taken together these findings indicate distinct inflammatory mechanisms are involved in arthritis and concomitant atherosclerosis, and neither process is dependent on CCR2.
To cite this abstract in AMA style:Montgomery AB, Cuda CM, Dominguez S, Mayr M, Winter DR, Perlman H. Arthritis and Atherosclerosis in KRN Ag7 Mice Involve Distinct Inflammatory Cell Populations and Are Independent of CCR2 [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/arthritis-and-atherosclerosis-in-krn-ag7-mice-involve-distinct-inflammatory-cell-populations-and-are-independent-of-ccr2/. Accessed December 4, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/arthritis-and-atherosclerosis-in-krn-ag7-mice-involve-distinct-inflammatory-cell-populations-and-are-independent-of-ccr2/