Abstract
IntroductionSynovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets in this process remains largely unknown. The main in vitro polarized macrophage subsets are classically (M1) and alternatively (M2) activated macrophages, the latter comprising interleukin (IL)-4 and IL-10 polarized cells. Here, we aimed to evaluate the polarization status of synovial macrophages in spondyloarthritis (SpA) and rheumatoid arthritis (RA).MethodsExpression of polarization markers on synovial macrophages, peripheral blood monocytes, and in vitro polarized monocyte-derived macrophages from SpA versus RA patients was assessed by immunohistochemistry and flow cytometry, respectively. The polarization status of the intimal lining layer and the synovial sublining macrophages was assessed by double immunofluorescence staining.ResultsThe expression of the IL-10 polarization marker cluster of differentiation 163 (CD163) was increased in SpA compared with RA intimal lining layer, but no differences were found in other M1 and M2 markers between the diseases. Furthermore, no significant phenotypic differences in monocytes and in vitro polarized monocyte-derived macrophages were seen between SpA, RA, and healthy controls, indicating that the differential CD163 expression does not reflect a preferential M2 polarization in SpA. More detailed analysis of intimal lining layer macrophages revealed a strong co-expression of the IL-10 polarization markers CD163 and cluster of differentiation 32 (CD32) but not any of the other markers in both SpA and RA. In contrast, synovial sublining macrophages had a more heterogeneous phenotype, with a majority of cells co-expressing M1 and M2 markers.ConclusionsThe intimal lining layer but not synovial sublining macrophages display an IL-10 polarized-like phenotype, with increased CD163 expression in SpA versus RA synovitis. These differences in the distribution of the polarized macrophage subset may contribute to the outcome of chronic synovitis.
Highlights
Synovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets in this process remains largely unknown
The number of CD68+ macrophages in the intimal lining layer and synovial sublining was similar between the two diseases (Figure 1A, D), whereas cluster of differentiation 163 (CD163) expression was higher in the SpA compared with the rheumatoid arthritis (RA) intimal lining layer (P < 0.05) (Figure 1B), but similar in the synovial sublining (Figure 1E)
The expression of the mainly by interferon (IFN)-g (MFIFN-g) marker CD64, the positive MFIL-4 marker CD200R, and the negative MFIL-4 marker CD14 was similar in the synovial sublining of SpA and RA (Figure 1G through 1I) and was very low to absent in the intimal lining layer
Summary
Synovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets in this process remains largely unknown. The main in vitro polarized macrophage subsets are classically (M1) and alternatively (M2) activated macrophages, the latter comprising interleukin (IL)-4 and IL-10 polarized cells. Tissue macrophages consist of resident macrophages and monocytes that are recruited in inflammatory conditions and differentiate into macrophages on tissue entry. These macrophages represent a heterogeneous population, as local mediators can prime macrophages during their maturation and thereby shape their subsequent response to various activating stimuli [15,16]. Two main polarized macrophage subsets were described based on their pro- versus antiinflammatory functions: classically activated macrophages (M1), which are specialized in the clearance of intracellular pathogens, and alternatively activated macrophages (M2), which have immunoregulatory properties and are involved in scavenging debris, angiogenesis, and tissue repair [17]. Whereas the macrophage polarization has been best described in rodents, we recently validated specific phenotypic markers [21] and distinct functional characteristics (unpublished observations) for these three main in vitro polarized macrophage subsets in humans
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