Intimal lining layer macrophages but not synovial sublining macrophages display an IL-10 polarized-like phenotype in chronic synovitis

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.

Among human macrophages polarised to different phenotypes, the M-CSF-oriented cells present the highest pro-inflammatory response to the rheumatoid arthritis-specific immune complexes containing ACPA

“…Histological analyses of biopsies showed that sublining macrophages had a heterogeneous phenotype because they co-expressed markers found on in vitro IFN-γ-polarised, IL-4-polarised or IL-10-polarised cells. In contrast, intimal lining layer macrophages revealed a strong co-expression of CD163 and CD32, leading the authors to propose that intimal macrophages displayed an IL-10-polarised-like phenotype 37. Since our data have highlighted the phenotypic overlap between the IL-10-exposed and the M-CSF-exposed cells, it could alternatively be proposed that the expression of these two markers results from an exposure to M-CSF.…”

“…However, the idea that the M-CSF-induced macrophage phenotype is common in RA joints is sustained by strong circumstantial evidence. Indeed, despite the current difficulties, the use of the specific markers of human macrophages described by Ambarus et al 29 has allowed a preliminary appraisal of the polarisation status of synovial macrophages in RA and spondyloarthritis 37. Histological analyses of biopsies showed that sublining macrophages had a heterogeneous phenotype because they co-expressed markers found on in vitro IFN-γ-polarised, IL-4-polarised or IL-10-polarised cells.…”

The prolactin receptor is expressed in rheumatoid arthritis and psoriatic arthritis synovial tissue and contributes to macrophage activation

“…2A–F). The presence of immunomodulatory cytokines and other factors in tissue can impact on gene expression and subsequent macrophage functional responses, a process referred to as polarization, and it has previously been shown that ST macrophages in inflammatory arthritis are phenotypically heterogeneous [41]. To determine which subtypes of macrophages express PRLR, we differentiated healthy donor monocytes under various polarizing conditions, including GM-CSF, IFN-γ, IL-10, M-CSF and RA SF.…”

IgM rheumatoid factor amplifies the inflammatory response of macrophages induced by the rheumatoid arthritis-specific immune complexes containing anticitrullinated protein antibodies

“…Conversely, when they accumulate in tissues, where they are notably met by macrophages endowed with a higher capacity of cytokine response, they are more likely to cause inflammation and the extra-articular manifestations to which they are associated 37. However, it should be stressed that our study only investigated the response of M-CSF-differentiated macrophages, taken as prototypic synovial tissue macrophages38 39 while macrophages can be phenotypically and functionally heterogeneous,40 and recent data suggest that different subpopulations of macrophages with different Fcγ receptor expression profiles coexist in the RA synovial membrane 41 42. It would therefore be interesting to compare the cytokine responses of differentially polarised macrophages to ACPA-IC.…”