PAQR11 modulates monocyte‐to‐macrophage differentiation and pathogenesis of rheumatoid arthritis

Abstract

Summary During inflammation or tissue injury, pro‐inflammatory mediators attract migratory monocytes to inflammatory sites and monocyte‐to‐macrophage differentiation occurs to activate macrophages. We report here that PAQR11, a member of the progesterone and AdipoQ receptor family, regulates monocyte‐to‐macrophage differentiation in vitro and in vivo. Paqr11 gene was highly induced during monocyte‐to‐macrophage differentiation. Knockdown or deletion of Paqr11 inhibited monocyte differentiation but had little effect on macrophage polarization. Mechanistically, PAQR11 promoted cell survival as apoptosis was increased by Paqr11 knockdown or deletion. Activation of the MAPK signalling pathway was involved in the regulatory role of PAQR11 on monocyte differentiation and cell survival. C/EBPβ regulated the expression of Paqr11 at the transcriptional level. In mice, deletion of Paqr11 gene alleviated progression of collagen‐induced rheumatoid arthritis. Thus, these results provide strong evidence that PAQR11 has a function in monocyte‐to‐macrophage differentiation and such function is related to autoimmune disease in vivo.

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“…The plasmid Laconic/pcDNA3.1 for lactate detection was purchased from Addgene. Slc16a1 deletion For Peer Review Only Diabetes in 3T3-L1 cells were carried out by lentivirus infection as previously reported (21). Lipo2000 was used in transient transfection for lactate detection in 3T3-L1 cells.…”

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“…Monocyte to macrophage differentiation-associated (MMD) protein is a member of the progestin and AdipoQ receptor (PAQR) family and was found in mature macrophages and reported to be associated with macrophage activation in vitro [38]. CD180, also known as RP105, is a cell surface molecule consisting of extracellular leucine-rich repeats (LLR) and a short cytoplasmic tail.…”

Can we treat inflammation by managing misbehaving monocytes?

“…They have, for instance, recently been demonstrated to play critical roles in controlling the switch between inflammatory responses and resolution in rheumatoid arthritis [6]. Here we highlight a recently published paper in Immunology that describes a new role for the molecule PAQR11 in the differentiation of monocytes as they enter the inflamed rheumatoid synovium [7]. The gene was initially identified by mRNA differential display as being expressed in macrophages, but not in freshly isolated monocytes [8], and has previously been described as a Golgi-localized regulator of Ras signalling [9], and as an important factor involved in the reorganization of the Golgi apparatus during metastatic transformation of tumour cells [10].…”

“…Here, Lin et al [7] report that the Paqr11 gene is expressed at high levels during monocyte differentiation and that Paqr11 knockdown leads to apoptosis of monocytes in vitro. Furthermore, in the collagen-induced arthritis mouse model of arthritis, Paqr11deficient mice displayed fewer signs of arthritis and less histological inflammation [7]. The authors conclude, therefore, that targeting monocyte-macrophage differentiation through PARQ11 may be a productive strategy for treating inflammatory arthritis and other autoimmune diseases.…”

“…The gene is expressed in human synovial macrophages [11]. Here, Lin et al [7] report that the Paqr11 gene is expressed at high levels during monocyte differentiation and that Paqr11 knockdown leads to apoptosis of monocytes in vitro. Furthermore, in the collagen-induced arthritis mouse model of arthritis, Paqr11deficient mice displayed fewer signs of arthritis and less histological inflammation [7].…”