Differential Accumulation and Activation of Monocyte and Dendritic Cell Subsets in Inflamed Synovial Fluid Discriminates Between Juvenile Idiopathic Arthritis and Septic Arthritis

Abstract

Despite their distinct etiology, several lines of evidence suggest that innate immunity plays a pivotal role in both juvenile idiopathic arthritis (JIA) and septic arthritis (SA) pathophysiology. Indeed, monocytes and dendritic cells (DC) are involved in the first line of defense against pathogens and play a critical role in initiating and orchestrating the immune response. The aim of this study was to compare the number and phenotype of monocytes and DCs in peripheral blood (PB) and synovial fluid (SF) from patients with JIA and SA to identify specific cell subsets and activation markers associated with pathophysiological mechanisms and that could be used as biomarkers to discriminate both diseases. The proportion of intermediate and non-classical monocytes in the SF and PB, respectively, were significantly higher in JIA than in SA patients. In contrast the proportion of classical monocytes and their absolute numbers were higher in the SF from SA compared with JIA patients. Higher expression of CD64 on non-classical monocyte was observed in PB from SA compared with JIA patients. In SF, higher expression of CD64 on classical and intermediate monocyte as well as higher CD163 expression on intermediate monocytes was observed in SA compared with JIA patients. Moreover, whereas the number of conventional (cDC), plasmacytoid (pDC) and inflammatory (infDC) DCs was comparable between groups in PB, the number of CD141 + cDCs and CD123 + pDCs in the SF was significantly higher in JIA than in SA patients. CD14 + infDCs represented the major DC subset in the SF of both groups with potent activation assessed by high expression of HLA-DR and CD86 and significant up-regulation of HLA-DR expression in SA compared with JIA patients. Finally, higher activation of SF DC subsets was monitored in SA compared with JIA with significant up-regulation of CD86 and PDL2 expression on several DC subsets. Our results show the differential accumulation and activation of innate immune cells between septic and inflammatory arthritis. They strongly indicate that the relative high numbers of CD141 + cDC and CD123 + pDCs in SF are specific for JIA while the over-activation of DC and monocyte subsets is specific for SA.

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

“…However, in the peripheral blood of mice, they are classified according to the expression of Ly6C and CD43: the classical (Ly6C ++ CD43 + ), the intermediate (Ly6C ++ CD43 ++ ), and the nonclassical (Ly6C + CD43 ++ ) ( 40 , 42 ). Based on this theory, it has been proposed that: the classical monocytes are the main origin of osteoclasts (differentiation under normal circumstances); in inflammatory environment, the intermediate monocytes are transformed into osteoclasts with high absorption potential; the non-classical monocyte differentiate into non-resorbable osteoclasts ( 43 – 46 ). These indicate that the monocytes/macrophages subpopulation is the determinant of the formation and function of osteoclasts, which needs further research to clarify.…”

Macrophage-Osteoclast Associations: Origin, Polarization, and Subgroups

“…On the basis of CD14 and CD16 antigens expression, monocytes are divided into three groups: classical (CD14 ++ CD16 − ), intermediate (CD14 ++ CD16 + ), and nonclassical (CD14 + CD16 ++ ) (29,30). According to this hypothesis, classical monocytes are the major source of osteoclasts, while intermediate monocytes can transform into high-absorption-capacity osteoclasts during inflammation, with non-classical monocytes evolving into non-resorbable osteoclasts (31)(32)(33)(34). The study has reported that the intermediate monocytes convert into M1macrophages to perform crucial functions in inflammation of the synovium.…”

Functional specialization of specific DC subsets in the synovial fluid of JIA patients

“…To fill this gap in knowledge, we have comprehensively profiled monocytes and cDC subsets in the exudate derived from the inflamed joint of JIA patients. Although SF from the joints of arthritis patients, may not be a complete reflection of the inflammation taking place in the tissue, it has proven to be an excellent model to study APC in a highly inflammatory environment 7,21 . Our findings show that at the site of inflammation, there is specific, functional programming of human DC subsets.…”

“…Although the maintenance of DC subsets is undergoing consistent dynamic change, monocytes, conventional DC (cDC) and plasmacytoid DC (pDC) are widely accepted as the most dominant APCs in steady state peripheral blood (PB) [4][5][6] . The PB DC subsets are defined as CD141 + cDC1, CD1c + cDC2 and CD123 + pDCs 7 . DCs are also present in tissues where they display a more mature phenotype than their blood counterparts 8,9 .…”